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To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities. • Polyelectrolyte coated liposomes were prepared via a single-step microfluidic method. • Quaternary chitosan coating increased uptake by 100-fold than those without coating. • AVA+cationic liposomes induce higher IgG anti-PA antibodies titers than AVA only. • Quaternary chitosan-coated liposomes act as both carriers and vaccine adjuvants. • We provides an innovative system for the development of new liposomal vaccines. [ABSTRACT FROM AUTHOR]

Bacterial infections pose a serious threat to human health, and the emergence of superbugs and the growing antibiotic resistance phenomenon have made the development of novel antimicrobial products. In this paper, an ultrasmall Cu, N co-doped carbon dots (CDs-Cu-N) with excellent peroxidase mimic activity and enhanced catalase mimic activity was successfully prepared and anchored to an injectable chitosan (CS)-based hybrid hydrogel. As expected, the CDs-Cu-N-H 2 O 2 -CS hybrid hydrogel maintains the excellent enzyme-mimicking properties of CDs-Cu-N and shows superior antibacterial property, which has been proven to effectively promote the healing of S. aureus -infected wounds with good biocompatibility. Benefitting from the dual-enzyme-mimic activity of CDs-Cu-N, the hybrid hydrogel not only can catalyze the generation of highly toxic ROS from low concentration of H 2 O 2 to inhibit the bacterial infections, but also can significantly promote the wound tissue repair and regeneration by improving the anoxic microenvironment and promoting neovascularization. In addition, this hybrid hydrogel also possessed excellent injectability and moldability. It can adapt to various the irregular shapes of acute wounds, maintaining a moist and safe microenvironment while prolonging the action time of nanozyme on wounds, thus promoting wound healing. This injectable hybrid hydrogel shows great potential applications in the field of wound infection management. • A simple strategy to prepare an injectable chitosan-based hybrid hydrogel incorporating a CDs-Cu-N nanozyme was proposed. • The CDs-Cu-N nanozyme possesses excellent peroxidase mimic activity and enhanced catalase mimic activity. • The CDs-Cu-N-H 2 O 2 -CS hybrid hydrogel showed nearly 100% antimicrobial effect against E. coli , S. aureus and C. albicans. • The CDs-Cu-N-H 2 O 2- -CS hybrid hydrogel have rapid wound self-healing ability and good injectability. • The CDs-Cu-N-H 2 O 2 -CS hybrid hydrogel exhibited great promise for in the field of wound infection management. [ABSTRACT FROM AUTHOR]

The controlled release of antioxidant substances at the intestinal oxidative damage site is crucial for alleviating intestine-related diseases. Herein, the novel ROS-responsive carrier was synthesized through simple amidation reaction between carboxymethyl chitosan (CMC) and methionine (Met), a natural organic compound containing ROS-responsive linkages (thioether). Initially, astaxanthin (AXT) nanoparticles (AXT 2 @CMT) with excellent stability and drug loading capacity (39.68 ± 0.23 μg/mL) were prepared by optimizing various reaction conditions. In the simulated high-concentration ROS environment of the intestine, CMT achieved a transition from hydrophobic groups (thioether) into hydrophilic groups (sulfone), which was conducive to the controlled release of AXT. In vitro cell experiments revealed that AXT 2 @CMT could effectively alleviate the oxidative damage in intestinal epithelioid cell line No. 6 (IEC-6 cell) caused by H 2 O 2. This study achieved a straightforward preparation of ROS-responsive nanocarrier through food ingredients, offering a theoretical foundation for the controlled release of AXT at the intestinal oxidative damage site. • Novel ROS-responsive carrier was synthesized by simple amidation reaction. • ROS-responsive behavior was realized by thioether in methionine. • The thioether in the carrier could be oxidized to sulfone by the ROS in the intestine. • The controlled release of astaxanthin was achieved under a high concentration of ROS. • The nanoparticles could effectively alleviate the oxidative damage in IEC-6 cells. [ABSTRACT FROM AUTHOR]

The use of hydrogels to mimic natural cartilage implantation can effectively solve the current problems of insufficient cartilage donors and low rate of injury healing. In particular, injectable hydrogels are less invasive in clinical applications and better able to fill uneven injury surfaces. Here, we prepared NorCS and CS-SH by modifying chitosan with 5-norbornene-2-carboxylic acid and N-Acetyl-L-cysteine, respectively. Dual-network hydrogels were prepared by using UV-triggered thiol-ene click reaction between NorCS and CS-SH and the metal coordination between SA and Ca2+. The prepared hydrogels can be cross-linked quickly and exhibit excellent degradability, self-healing and injectable properties. At the same time, the hydrogel also showed good cytocompatibility and could significantly restore the motor function of mice. This study provides an effective strategy for preparing injectable hydrogels capable of rapid cross-linking. • Two novel chitosan derivatives containing norbornene and sulfhydryl were synthesized. • Coordination bonds give hydrogels stability, self-healing and injectable properties. • By adjusting the proportion of different components in the hydrogel, the performance of the hydrogel can be adjusted. • The synthesized hydrogels have good biocompatibility and have potential for cartilage repair. [ABSTRACT FROM AUTHOR]

The delay of diabetic wound healing puts a huge burden on the society. The key factors hindering wound healing include bacterial infection, unresolved inflammation and poorly generated blood vessels. In this paper, glycidyl trimethyl ammonium chloride (GTA) was grafted to chitosan (CS) to obtain quaternary ammonium grafted chitosan (QCS) with enhanced antibacterial performance, and then cross-linked by dialdehyde terminated poly(ethylene oxide) (PEO DA) to construct QCS/PEO DA hydrogel with tissue adhesion, biodegradation and self-healing properties. The QCS/PEO DA hydrogel is loaded with tannin acid (TA) and deferoxamine (DFO) to enhance antioxidant property and angiogenesis. At the same time, the TA and DFO loaded TA@DFO/hydrogel preserved the biocompatibility and biodegradability of chitosan. Moreover, the multifunctional hydrogel behaved excellent hemostatic properties in mice model and significantly promoted the healing efficacy of diabetic wounds. Overall, the TA@DFO/hydrogel is promising anti-infection dressing material for diabetic wound healing. • GTA was grafted to chitosan to prepare QCS with enhanced antibacterial performance. • The QCS was cross-linked PEO DA to construct self-healing hydrogel with tissue adhesion and biodegradability. • The QCS/PEO DA hydrogel is loaded with TA and DFO to enhance antioxidant property and angiogenesis. • The TA@DFO/hydrogel behaved excellent hemostatic properties and promoted diabetic wound healing. • The TA@DFO/hydrogel is a promising anti-infection wound dressing material. [ABSTRACT FROM AUTHOR]

Increased glycine concentrations are associated with altered metabolism of cancer cells and is reflected in the bodily fluids of the brain cancer patients. Various studies have been conducted in past to detect glycine as an imaging biomarker via NMR Spectroscopy tools. However, the use is limited because of the low concentration and different in vivo detection due to overlapping of peaks with myo-inositol in same spectral position. Alongside, little is known about the electrochemical potential of Glycine as a biomarker for brain cancer. The prime impetus of this study was to check the feasibility of glycine as non-invasive biomarker for brain cancer. A divergent approach to detect glycine "non-enzymatically" via unique chitosan lecithin nanocomposite has been utilised during this study. The electrochemical inactivity at provided potential that prevented glycine to get oxidized or reduced without mediator was compensated utilising the chitosan-lecithin nanocomposite. Thus, a redox mediator (Prussian blue) was used for high sensitivity and indirect detection of glycine. The chitosan nanoparticles-lecithin nanocomposite is used as a matrix. The electrochemical analysis of the onco-metabolomic biomarker (glycine) utilizing cyclic voltammetry in glycine spiked multi-Purpose artificial urine was performed to check distribution of glycine over physiological range of glycine. A wide linear range of response varying over the physiological range from 7 to 240 μM with a LOD 8.5 μM was obtained, showing potential of detection in biological samples. We have further evaluated our results via simulating the interaction of mediator and matrix with Glycine by HOMO-LUMO band fluctuations. • Developed Prussian Blue , Chitosan-lecithin nanocomposite todetect glycine. • Detection of electro inactive metabolite (Glycine) utilising Redox Active Reporter. • Non-enzymatic detection of glycine as a pediatric brain cancer biomarker in multi-Purpose artificial urine. • EC Detection of glycine with LOD of ∼8.5 µM covering the physiological range from 7 to 240 µM. • Simulation study for detailed insights in EC interaction of nanocomposite matrices with glycine. [ABSTRACT FROM AUTHOR]

The current situation of diabetes prevention and control is extremely severe. For instance, glimepiride (GLM), a third-generation sulfonylurea, demonstrates suboptimal clinical efficacy in oral dosage forms, which underscores the pressing need for the development of a new dosage form. Recently, in situ gel subcutaneous implants have garnered considerable attention. Hydroxybutyl chitosan (HBC) can spontaneously crosslink to form a thermosensitive hydrogel and has good biocompatibility. However, its application is hindered by its limited mechanical properties. Graphene oxide (GO), known for its stable dispersion in water, can load GLM through π–π stacking interactions. When combined with HBC, GO enhances the mechanical properties and stability of the hydrogel. Therefore, an HBC–GO@GLM hydrogel was prepared. Rheological analysis revealed that the incorporation of GO increased the critical gelation temperature of the 5 wt% HBC hydrogel from 19.1°C to 27.2°C, considerably enhancing the mechanical properties of the hydrogel. Using encapsulation efficiency as an evaluation index, the optimal encapsulation efficiency of GO@GLM was determined to be 73.53% ± 0.45% with a drug loading capacity of 27.39 ± 0.17% using the Box–Behnken design model. Computer simulation technology validated the interaction between the materials and the drug release mechanism. Pharmacokinetic results showed that compared to the HBC@GLM group, the half-life (t1/2), mean residence time and the area under the curve for the HBC–GO@GLM group were approximately 3 times those of the HBC@GLM group. Subcutaneous implantation of the HBC–GO@GLM hydrogel for drug delivery considerably extended the drug's action time in the body, thereby maintaining blood sugar levels within a normal and stable range for an extended period. [Display omitted] • The introduction of GO enhances the drug-carrying capacity of HBC hydrogels. • HBC-GO drug delivery system for sustained and slow drug release. • Improved bioavailability of glimepiride (GLM). • Computer simulation explained the interaction mechanism between drug and carrier. • HBC-GO@GLM has good biodegradability and biocompatibility. [ABSTRACT FROM AUTHOR]

In this study, cross-linked carboxymethyl cellulose/chitosan submicron particles were employed to facilitate the stabilization of Pickering emulsion. The polymer particles were prepared using the polyelectrolyte self-assembly method in conjunction with isocyanide based multicomponent reactions and the characteristics were obtained using: nuclear magnetic resonance, Fourier-transform infrared spectroscopy and dynamic light scattering. Atomic force microscopy revealed the heterogeneous structure of the resulting submicron particles with domains of 20–30 nm in size. The average diameter was found to be in the range of 229–378 nm and they were found to be suitable for the fabrication of oil/water Pickering emulsion when proceeded via the homogenization method followed by sonication. The results obtained revealed that carboxymethyl cellulose/chitosan particles significantly stabilized the droplets at the oil/water interface. Even at low particle concentrations of 0.3 g/L (which is close to that of low molecular weight surfactants) stable Pickering emulsions have been obtained. Additionally, the resulting emulsions showed a high level of stability with regard to changes in pH, temperature and ionic strength. The natural alkaloid piperine was used as a model compound to load the resulting particles, which possessed encapsulation efficiency of 90.6±0.4%. Furthermore, the in vitro release profile of piperine from the Pickering emulsion revealed a much-controlled release in both acidic and neutral media as compared to the unformulated piperine. Additional findings in this work revealed important information on the application of carboxymethyl cellulose/chitosan submicron particles as Pickering stabilizers for creation of new delivery systems. [Display omitted] • CMC/chitosan submicron particles stabilize Pickering emulsions at low concentrations. • AFM microscopy revealed the domain structure of CMC/chitosan particles. • Reaction between chitosan, CMC, formaldehyde and diisocyanide forms 3-D structure. • Pickering emulsions stabilized by CMC/chitosan particles are sensitive to Ca2+ ions. [ABSTRACT FROM AUTHOR]

This work aims at improving and disclosing new properties of films based on polylactic acid (PLA) and a star-shaped polycaprolactone (PCL). Indeed, previous works demonstrated that the presence of ad-hoc synthesized PCL, characterized by low molecular weight and carboxyl end groups (coded as PCL-COOH), improves the elongation at break of the films compared to that of neat PLA and increases their functionality. To further improve the properties of the system, alternating layers of chitosan (CH) and DNA were deposited on the surface applying a Layer-by-Layer (LbL) technique. This method was chosen because it allows the properties of the system to be modified without affecting the specific features of the bulk. In addition, the LbL technique is easily scalable and environmentally friendly because it is based on the use of an aqueous solution of two biomaterials, namely DNA and CH, which are not only derived from renewable sources but are also biocompatible and biodegradable. IR measurements on model silicon substrates subjected to the same treatment as the films, pointed out a linear growth of the proposed LbL assembly. Indeed, FE-SEM measurements highlighted the deposition of a uniform coating. The presence of the CH/DNA assembly reduced the oxygen permeability under both dry and humid (50% R.H.) conditions when compared to the uncoated film. In addition, the coating had no relevant effect on the hydrolytic and enzymatic degradation of the system, so that the biodegradability of the film was maintained. • Films based on polylactic acid and a star-shaped polycaprolactone are used. • Alternating layers of CH and DNA were deposited on the film surface by LbL. • The presence of the CH/DNA assembly reduced the film oxygen permeability. • The biodegradability of the coated films is maintained. [ABSTRACT FROM AUTHOR]

Irinotecan (CPT-11) is used as a first or second-line chemotherapy drug for the treatment and management of colorectal cancers. In vitro studies have shown that 7-ethyl-10-hydroxycamptothecin (SN38), the active metabolite of CPT-11, displays promising anticancer efficacy. However, its poor aqueous solubility and hydrolytic degradation result in its lower oral bioavailability and impracticable clinical application. To overcome these limitations, a novel amphiphilic chitosan derivative, deoxycholic acid decorated N'-nonyl-trimethyl chitosan, was synthesized. Nano-micelles loaded with SN38 were subsequently prepared to enhance the bioavailability and anti-tumor efficacy of the drug through oral administration. The nano-micelles demonstrated improved dilution stability, enhanced greater mucosal adherence, significant P-gp efflux inhibition, and increased drug transport in the intestine by paracellular and transcellular pathways. Consequently, both the in vivo pharmacokinetic profile and therapeutic efficacy of SN38 against cancer were substantially improved via the micellar system. Thus, the developed polymeric micelles can potentially enhance the SN38 oral absorption for cancer therapy, offering prospective avenues for further exploration. • Novel chitosan derivative, N-Deoxycholic acid grafted N'-nonyl-trimethyl chitosan, enabled nano-micelle assembly. • Stable micelles loaded with SN38 were prepared for improving its oral delivery. • The micelles exhibited enhanced mucosal adhesion, P-gp inhibition, and intestinal drug transport. • Micellar system improved the oral bioavailability and anticancer efficacy of SN38. [ABSTRACT FROM AUTHOR]

Dasatinib (DST) is a tyrosine kinase inhibitor with established antiproliferative activity in Triple-negative breast cancer. Conventional treatment strategies with DST have several pitfalls related to the development of resistance, lower cellular uptake and unwanted adverse effects. To address these issues, we have prepared P-selectin-targeted nanoparticles of DST with fucoidan (FUC) as a ligand. Poly lactide-co-glycolide nanoparticles of DST were coated with chitosan (CH) and FUC via electrostatic interaction (DST-CH-FUC-NPs). The mean particle size of 210.36 ± 0.66 nm and a polydispersity index of 0.234 ± 0.013 was observed for DST-CH-FUC-NPs. TEM and FTIR analysis proved CH coating followed by an FUC layer on nanoparticles. DST-CH-FUC-NPs showed a sustained release profile up to 120 h and 2.9 times less hemolytic potential than free DST suspension. DST-CH-FUC-NPs demonstrated 8-fold higher cytotoxicity compared to free DST in MDA-MB-231 cells. Rhodamine-CH-FUC- NPs showed 19 times and 3 times higher cellular uptake than free Rhodamine and Rhodamine-CH-NPs, respectively. DST-CH-FUC-NPs also displayed increased ROS production and mitochondrial membrane potential damage. Apoptosis study revealed a 7.5-fold higher apoptosis index for DST-CH-FUC-NPs than free DST. Subsequently, the DST-CH-FUC-NPs showed increased inhibition of cell migration, where approximately 5 % wound closure was noted. Further, DST-CH-FUC-NPs confirmed higher disruption of lysosomal membrane integrity, which is well correlated with apoptosis results. In addition, developed NPs were nontoxic on MCF 10 A normal cells. All these findings suggest that fabricated DST-CH-FUC-NPs are promising biocompatible carriers for tumor-targeted delivery and enhanced efficacy of dasatinib. [Display omitted] • P-selectin receptors are actively targeted using FUC ligand. • DST-CH-FUC-NPs were prepared by electrostatic interaction. • FUC coating enhanced cytotoxicity potential in MDA-MB-231 cells. • DST-CH-FUC-NPs increased apoptosis and ROS generation. • DST-CH-FUC-NPs showed higher mitochondrial membrane depolarization. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria in drinking water threaten human health and life. In the work, antimicrobial films composed of myricetin@tannic acid (My@TA) nanoparticles (NPs) and chitosan derivation microgels were developed to kill pathogenic bacteria in drinking water. Hydrophobic My was first made into water soluble My@TA NPs using a solvent exchange method with TA as stabilizer. Polymeric microgels of carboxymethyl chitosan (CMCS)/hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were then fabricated with a blending method. CMCS&HACC/My@TA multilayer films were further deposited on the internal surface of PET bottles by using a layer-by-layer (LbL) assembly technique. The PET bottles coated with the films could effectively kill pathogenic bacteria in water such as S. aureus , E. coli , Staphylococcus epidermidis , Pseudomonas fluorescens , Listeria monocytogenes and methicillin resistant Staphylococcus aureus (MRSA). In addition, CMCS&HACC/My@TA films displayed good antioxidant activity, water resistance, and in vivo biocompatibility with heart, liver, spleen, lung and kidney organs. We believe that the container coated with CMCS&HACC/My@TA films can be applied to prevent microbial contamination of drinking water. [Display omitted] • Hydrophobic My was made into water soluble NPs using solvent exchange method. • CMCS&HACC/My@TA films were prepared using LbL assembly technique. • CMCS&HACC/My@TA films could kill multiple pathogenic bacteria in water. • CMCS&HACC/My@TA films exhibited good antioxidant activity and water resistance. • CMCS&HACC/My@TA films had good in vivo biocompatibility. [ABSTRACT FROM AUTHOR]

Naso- and oropharyngeal swabs are the Center for Disease Control and Prevention (CDC) -recommended disease sampling methods for respiratory viruses. The short swabbing time for sampling by these methods may lead to variability in test results. Further, these methods are mildly invasive and can cause discomfort, tearing or gag reflexes in tested individuals. If longer sampling time is coupled with lesser patient discomfort, test reliability and patient compliance can be improved. Towards this end, we developed cationic biopolymer membranes for the electrostatic capturing of viruses in the oral cavity. Here, chemically (EDC-NHS) crosslinked uncharged chitosan (CS) nanofiber membranes were conferred either with negative surface charge by anionic poly-aspartic acid (pAsp) coating or positive charge by cationic poly- L -lysine (PLL). Consistent with our preliminary findings of dynamic light scattering (DLS) size measurements showing large agglomerates of anionic virus-like particles (VLPs) and cationic PLL in solution, a 75% increase in VLP adsorption by PLL coated CS membranes was recorded by enzyme linked immunosorbent assay (ELISA), in comparison to untreated controls. It is envisaged that the electrostatic concentration of respiratory viruses on cationic membranes can be superior alternatives to traditional swabbing in the oral cavity. [Display omitted] • Chitosan nanofiber membranes surface coated with poly- L -lysine (PLL) are cationic. • HIV-1 Gag virus-like particles (VLPs) are anionic in physiological media. • Electrostatic capture of VLPs by cationic PLL was demonstrated by DLS and p24 ELISA. • SARS-CoV-2 Spike protein incorporated VLPs were poorly detected by COVID19S2 ELISA. • Cationic biopolymer membranes are proposed as alternatives to traditional oral swabs. [ABSTRACT FROM AUTHOR]

In this study, a pH-responsive hydrogels based on laponite rapid dispersion (Lap®)/chitosan (CS)/polyvinyl alcohol (PVA) designed and was used for controlled delivery of the anticancer drug curcumin (CUR). First, it was accomplished by dissolving CUR in Lap® dispersion under the influence of the pH of the environment. Then, in the presence of Lap®CUR cross-linking was incorporated between CS and PVA polymers. The structural features of Lap®CUR/CS@PVA hydrogels are characterized using FT-IR, XRD, SEM/EDS, TEM, TGA, Zeta potential, and XPS. The in vitro drug release profiles confirmed a pH-responsive controlled release of CUR in acidic pH for all hydrogels. During 12 h, the cumulative release of CUR from Lap®CUR/0.1CS@PVA hydrogel was 27.9% and 12.3%, at pH 5.5 and 7.4, respectively. While during three days the release rate reached 48.5% and 18.5%. The CUR release kinetic from hydrogels also suggests that the kinetic data well fitted to the Korsmeyer-Peppas, diffusion-controlled and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that Lap®CUR/0.1CS@PVA hydrogel had lower cytotoxicity than CUR against MDA-MB 231 cancer cells, which confirmed the controlled release of drug through hydrogels. Meanwhile, in vitro hemolysis, antioxidant and antibacterial tests revealed that the prepared hydrogels have good blood compatibility, excellent antioxidant properties, and antibacterial activity. Based on the obtained results, the designed hydrogels could be potentially applied as pH-controlled drug delivery systems for cancer therapy. [Display omitted] • pH-responsive hydrogels based on laponite/chitosan/polyvinyl alcohol were designed. • Curcumin was dissolved in the laponite dispersion under the influence of the pH. • Sustained release of curcumin from the carriers was obtained under the influence of pH. • The hydrogels showed cytotoxicity to the cancer cell line (MDA-MB 231). [ABSTRACT FROM AUTHOR]

• Chitosan nanoparticles containing lemongrass oil developed as nanogel by incorporating acrylate as a thickener. • The use of acrylate turns out as effective fabric binder and delivered improved wash durability. • The nanogel treated fabric exhibited excellent mosquito repellency after15 wash cycles. • Nanogel did not show any sign of dermal toxicity on Swiss albino mice. Chitosan nanocapsules, containing lemongrass (Cymbopogon citratus) oil (LGO), have been developed in gel form in which acrylate (Ac) was incorporated as a thickener and fabric binder. The gel was impregnated on fabric to achieve long-lasting and wash-durable mosquito repellency. The interaction between cotton fibers and gel was investigated by FTIR and XRD. Wash durability of gel was compared with chitosan nanocapsules without acrylate (LGO-encap) using SEM and GC-MS. The SEM analyses revealed that acrylate containing nanocapsules retains on fabric after a series of washing. The GC-MS results indicated that the relative amount of deducible oil components from fabric was found to be higher after the series of washing in acrylate containing nanocapsules (LGO-encap-Ac), which further points to the improved wash durability and retention of capsules on fabric. The bio-efficacy results of post-fifteen washing turned out was 75% of repellency against mosquitoes with the use of acrylate; while in nanocapsules without acrylate, only 51% of repellency was achieved. Furthermore, the 36 days repeated application of nanogel on Swiss albino mice did not show any signs of dermal toxicity. The formulation is, thus, suitable to impregnate dress of the military personals and individuals who have to perform field duty and where risk of mosquito bites is probably more. [ABSTRACT FROM AUTHOR]

• Multilayer films based on cationic chitosan and anionic alginate. • Polysaccharides-based capsules have been elaborated by a core-mediated LbL approach. • Complementary approach to classical nanoparticles based on chitosan. • The bacteria inhibition depends on the flexibility of the nanomaterial. Creating an appropriate antibacterial disinfection system without forming any harmful compounds is still a major challenge and calls for new technologies for efficient disinfection and microbial control. Towards this aim, we report on the elaboration of biodegradable and biocompatible polymeric nanocapsules, also called hollow nanoparticles, for potential applications in antibiotic therapy. These nanomaterials are based on the self-assembly of charged polysaccharides, namely chitosan and alginate, onto gold nanoparticles as a sacrificial matrix (60 nm). Electrostatic interactions between the protonated amine groups of chitosan (+35 mV) and the carboxylate groups of alginate (- 20 mV) are the driving attraction force enabling the elaboration of well-ordered multilayer films onto the spherical substrate. The removal of the colloidal gold, via cyanide-assisted hydrolysis, is evidenced by time-dependent variation of the gold spectroscopic signature (30 min is required). TEM shows the obtention of nanocapsules. An inhibitory effect of these particles has been demonstrated during the growth of two representative bacteria in a liquid medium: Staphylococcus aureus (Gram-positive) (from 4.6% to 16.3% for gold nanomaterials + and from 18.6% to 34.9% for (chi+/alg−) n -chi+ nanocapsules) and Escherichia coli (Gram-negative) (from 5.4% to 20% for gold nanomaterials and from 23.7% to 40% for (chi+/alg−) n -chi+ nanocapsules). Acridine orange staining demonstrated the bactericidal effect of chitosan-based capsules. These findings demonstrate that (chitosan/alginate) n capsules can be exploited as new antibacterial material. Thus, we present a complementary approach to classical nanoparticles prepared by complexation between alginate and chitosan or other materials. [ABSTRACT FROM AUTHOR]

• Interaction between biosurfactants and chitosan has additive action against S. mutans. • Interaction between biosurfactants and sodium fluoride has indifferent action toward S. mutans. • Toothpaste with biosurfactant and chitosan/sodium fluoride inhibited S. mutans biofilm. • Toothpaste with biosurfactant and chitosan/sodium fluoride is non-toxic. The aim of the present study was to formulate toothpastes containing biosurfactants and either fungal chitosan or sodium fluoride and evaluate the cytotoxicity, antimicrobial action and inhibition potential against biofilm formed by Streptococcus mutans. Chitosan was extracted from the biomass of the fungus Mucorales. We tested biosurfactants produced by Pseudomonas aeruginosa UCP 0992 (PB), Bacillus metylotrophicus UCP 1616 (BB) and Candida bombicola URM 3718 (CB). Fractional inhibitory concentration analysis was performed to determine the type of interaction between the compounds. Six toothpaste were prepared, the active ingredients of which were the biosurfactants, chitosan or sodium fluoride. The cytotoxicity tests were performed using the 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2- H -tetrazolium bromide (MTT) assay for the L929 (mouse fibroblast) and RAW 264.7 (mouse macrophage) cell lines. The toothpastes were tested with regard to pH, consistency and foaming capacity. The inhibition of biofilm was investigated by applying the toothpaste to biofilm formed in modified artificial saliva for 24 h at 37 °C in anaerobiosis. All substances had a minimum inhibitory concentration (MIC) for S. mutans. The combinations of CB and PB with chitosan had an additive effect against S. mutans , whereas BB combined with chitosan had an indifferent effect. The toothpastes were non-toxic. The formulations had pH around 9, spreading capacity between 8 and 17 mm and foaming capacity between 63 and 95%. All formulations inhibited the cellular viability of S. mutans in the biofilm, with similar results compared to the commercial toothpaste tested. The present results show that the formulations suggested are promising when compared to a commercial tooth paste. [ABSTRACT FROM AUTHOR]

• Chitosan crosslinked with THPC provides release of ciprofloxacin for six days. • Ciprofloxacin into chitosan hydrogels can be useful to treat superficial joint infections. • Chitosan hydrogels for superficial joint infections can be considered safe. Development of a pharmaceutical form for the superficial infections related with arthroplasties would be helpful for clinical practice. In this context, we set out to evaluate ciprofloxacin and gentamicin elution from systems based on chitosan. Films and semisolid hydrogels containing chitosan alone (2%) or in combination with gelatin (6%) or different proportions (from 12% to 36%) of tetrakis-(hydroxymethyl)-phosphonium-chloride (THPC) were tested as delivery systems. Different antibiotic doses were assayed (0.5 mg/cm2,1 mg/cm2 and 2 mg/cm2). Antibiotic release was studied for each formulation. In vitro cytocompatibility studies and a simulation exercise for bioactivity evaluation were performed. Samples containing chitosan or chitosan-gelatin released the antibiotics at very high rates. On the contrary, ciprofloxacin released was kept for 6 days from THPC-chitosan films and hydrogels. From hydrogel formulations release could be changed by varying the percentage of THPC. The system containing 12%-THPC-chitosan with 2 mg/cm2 of ciprofloxacin showed that 100% of patient would be covered during 72 h post-surgery. The concentration of 12%-THPC did not show cytotoxicity in NIH3T3 mouse fibroblasts after 48 h. THPC is suitable as crosslinker for chitosan when ciprofloxacin is incorporated showing a sustained release during 6 days. [ABSTRACT FROM AUTHOR]

• Sol to gel transition of developed formulation occurred above the room temperature. • Chitosan enhanced the mucoadhesive property of Poloxamer 407 based in situ gel. • Enhanced bioavailability and antidepressant activity of agomelatine. The current study was designed to enhance the brain bioavailability and to extract maximum therapeutic benefit from a novel antidepressant drug, agomelatine. For this purpose, a thermoresponsive in situ gel was prepared by dissolving 20% w/v of Poloxamer-407 in agomelatine containing nanoemulsion. To impart mucoadhesive property, 0.5% w/v concentration of chitosan was ensured in the final formulation, named as Ago-NE-gel+0.5%chitosan. The gelling point and mucoadhesive strength of Ago-NE-gel+0.5%chitosan were found to be 28 ± 1 °C, and 6246.27 dynes/cm2 respectively. The size of free micelles of Poloxamer-407 was recorded graphically at 18.43 ± 0.95 nm whereas the size of sterically stabilized Ago-NE was observed at 142.58 ± 4.21 nm. The viscosity and pH of Ago-NE-gel+0.5%chitosan were found to be 2439 ± 23 cP (at 35 ± 1 °C temperature) and 5.8 ± 0.2 respectively. The developed formulation was found safe on nasal mucosa during the toxicity study. CLSM based brain distribution study suggested that Ago-NE-gel+0.5%chitosan is more competent to deliver the drug into the brain as compared to agomelatine-suspension. After intranasal administration of Ago-NE-gel+0.5%chitosan in Wistar rats, the AUC 0-8h in brain and plasma were found to be 1418.591 ± 71.87 and 473.901 ± 32.42 ng.h/ml respectively. The hypothesis conceived at the beginning of this research work was delivered as 2.82 folds enhanced bioavailability of agomelatine in the brain. The behavioral studies confirmed that the antidepressant activity of agomelatine can be improved by loading the drug into a mucoadhesive-nanoemulsion-gel system followed by its intranasal administration. [ABSTRACT FROM AUTHOR]

• Correlation between electrical/antibacterial properties of CS/Cu films were done. • Cu chelation-induced mechanism during the Cu NPs formation in CS during synthesis. • Electrical conductivity demonstrates percolation threshold at CuNPs volume fraction ca. 0.00143. • Percolation threshold and saturation in antibacterial activity depends of CuNPs concentration. Correlation between electrical and antibacterial properties of chitosan/copper nanocomposites (CS/CuNPs) is investigated. We aim at achieving the minimum CuNPs concentration in a CS-matrix while keeping high antibacterial activity. UV–vis, TEM and XRD measurements confirms the formation of polygonal metallic CuNPs (ca. 30–50 nm). Interactions between NH 2 /OH groups of CS and CuNPs were determined by FTIR and XPS suggesting Cu chelation-induced mechanism during the CuNPs formation. DC electrical conductivity measurements reveals a percolation threshold at CuNPs volumetric concentration of ca. 0.143%. Antibacterial assays against Gram-positive bacteria and DC measurements helps correlate the antibacterial potency to the electron transfer between the negatively charged bacteria and CuNPs. Our study suggests that nanocomposite's maximum antibacterial activity is obtained below the electrical percolation threshold at extremely low CuNPs concentrations; this fact may prove useful in the design of nontoxic nanocomposites for biomedical applications. [ABSTRACT FROM AUTHOR]

• Preparation of Xylan/Chitosan/Montmorillonite porous scaffold by freeze drying. • Increase in pore size of scaffold on increasing MMT content up to 4%. • Ca/P ratio of 1.67 in SBF deposited apatite was achieved at 2% MMT concentration. • Needle like apatite morphology was observed in SBF at 5% MMT concentration. • Scaffolds possessed cell attachment tendency. The present study reports the fabrication of Xylan/Chitosan/Montmorillonite (MMT) composite scaffold by freeze drying process with the aim of achieving improved properties for bone tissue engineering applications. The scaffolds were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and mechanical testing. The fabricated scaffolds were found to be highly porous with variations in pore size (102 μm–290 μm) on varying the filler concentration. XRD study revealed complete exfoliation of MMT incorporated in polymer conjugates (Xylan/Chitosan) prepared by Maillard reaction. In-vitro bio-mineralization study revealed significant apatite deposition on polymer matrix. Scaffolds with 5% MMT concentration exhibited needle like morphology of deposited apatite which can further provide synergistic response in increasing the mechanical properties of scaffolds when placed in contact with body fluid. The average length and thickness of apatite needles were calculated to be 140 μm and 1.2 μm respectively. The deposited apatite crystals on scaffold with 2% MMT content demonstrated Ca/P ratio of 1.67, resembling that of natural bone apatite. Swelling and biodegradation behavior of scaffold were also studied with regard to hydrophilic and barrier effect of MMT on composites. MTT assay revealed non-cytotoxic nature of scaffold with good cell viability. [ABSTRACT FROM AUTHOR]

• Tri-layers nanofibers were synthesized via triaxial electrospinning process. • DOX, PTX and 5-FU anticancer drugs were simultaneously loaded into fibers. • 5-FU release from tri-layers nanofibers followed by zero-order kinetic model. • More than 94% MCF-7 breast cancer cells were killed using tri-layers fibers. In the present study, the tri-layer nanofibers were synthesized via triaxial electrospinning process to control the sustained delivery of Doxorubicin (DOX), Paclitaxel (PTX) and 5- fluorouracil (5-FU) anticancer drugs from nanofibers. The 5-FU molecules were incorporated into the core solution (chitosan/polyvinyl alcohol (CS/PVA)) to fabricate the CS/PVA/5-FU inner layer of nanofibers. The intermediate layer was prepared from poly(lactic acid)/chitosan (PLA/CS) nanofibers. The DOX and PTX molecules were initially loaded into the g-C3N4 nanosheets and following were incorporated into the PLA/CS solution to fabricate the outer layer of nanofibers. The synthesized nanosheets and nanofibers were characterized using XRD, SEM, TEM and UV–vis analysis. The PLA/PVA/CS/FU/g-C3N4/DOX/PTX single layer nanofibers were also synthesized via electrospinning method. The drug loading efficiency, degradation rate and anticancer drugs release profiles from single layer and tri-layer nanofibers were investigated under various intermediate and shell layer thicknesses. The pharmacokinetic studies were performed to understand the drugs release mechanism from nanofibers. The cell viability and cell attachment of drug loaded single layer and tri-layer nanofibers toward the MCF-7 breast cancer cells were examined to achieve an optimum nanofibrous formulation for the breast cancer treatment. The obtained results revealed the high activity of tri-layer nanofibers for the breast cancer cells killing. [ABSTRACT FROM AUTHOR]

• Chitosan-silica hybrid coating for metal stents was fabricated by sol-gel method. • The coating had robust mechanical stability and good adhesive strength. • The coated Co-Cr stent showed improved wettability and corrosion resistance. • The hybrid coating enabled efficient loading and sustained release of sirolimus. • The hybrid coat had excellent cytocompatibility and hemocompatibilty. The surface characteristics of coronary stents play a pivotal role in inhibiting in-stent restenosis and late-stent thrombosis. In this study, a sol-gel-derived silica xerogel-chitosan hybrid coating was applied to Co-Cr stent and was reported, for the first time, as a biocompatible drug delivery tool in vascular stent application. A dense and uniform chitosan-silica xerogel hybrid coating (<1-μm thick) was applied on bare Co-Cr material. Sirolimus was well incorporated into the hybrid coatings without re-crystallization. The chitosan-silica hybrid coating with 30 wt% silica xerogel showed better mechanical stability and good adhesive strength without any cracking or delamination. The chitosan-silica hybrid coated Co-Cr surface exhibited significantly improved wettability and corrosion resistance compared to the chitosan coated Co-Cr surface. In addition, the hybrid coating layer enabled efficient loading of sirolimus, owing to the unique mesoporous structure of silica xerogel, which further allowed the sustained release of sirolimus over 3 weeks. In-vitro tests with human umbilical cord vein endothelial cells and blood platelets confirmed that the chitosan-silica hybrid coating had excellent cytocompatibility and hemocompatibilty. Thus, this study demonstrated that the chitosan-silica hybrid material is a promising material for coating coronary stents, with minimal risk of in-stent restenosis and thrombogenicity. [ABSTRACT FROM AUTHOR]

• Amphiphilic chitosan was prepared by grafting deoxycholic acid and N-acetyl-L-cysteine. • Three kinds of drug-loaded nanomicelles were prepared via different deoxycholic acid grafting rates. • The higher the graft rate of deoxycholic acid, the more obvious the inhibition rate on the proliferation of A549 cells. Quercetin (QCT) has important functions such as antioxidant, anti-inflammatory and anticancer. However, its applications in food and in drug are restricted owing to its poor water solubility. In this work, a novel amphiphilic wall-material chitosan was synthesized via grafting of chitosan with deoxycholic acid (DA) as hydrophobic group and modified N-acetyl-L-cysteine (NAC) as hydrophilic group. Amphiphilic chitosan was self-assembled to load QCT as nanomicelles by a low-cost and inorganic solvent procedure. Both the encapsulation efficiencies (EE) and drug-loading rates (DL) increased when increasing the grafting rate of DA. There was a bursting release of QCT for the QCT-loaded nanomicelles (CS-DA-NAC-QNMs) from 0 to 8 h, and then the release rate decreased gradually. After releasing for 72 h, the final cumulative release percentages were more than 40%. All the QCT-loaded nanomicelles samples showed good hemocompatibility, and their water solubility and biocompatibility increased evidently. What's more, they exhibited an obvious inhibition rate of A549 cells. [ABSTRACT FROM AUTHOR]

• Iron oxide nanoparticles can be prepared in situ using chitosan gels. • Amount of inorganic phase rather decreased with increase in cross-linking density. • Heat-generation property was not governed solely by the total amount of iron oxide. • This study gives fundamental design of heat-generating hybrids for hyperthermia. Magnetic iron oxides such as magnetite and γ-hematite have attracted considerable attention as thermoseeds for hyperthermia treatment because of their ability to generate heat under an alternating magnetic field. Control of the particle size and their combination with biocompatible polymers are expected to be beneficial for optimization of the nanoparticles. These processes can be accomplished through the synthesis of magnetite in gels, as the network structure of the polymer gel can control the grain growth of the magnetite. However, the effect of the cross-linking density of the gels remains unclear. In this study, we synthesized magnetic iron oxides in situ in chitosan hydrogels with different cross-linking densities and examined the crystalline structure and heat generation under alternating magnetic field. The crystalline phase and amount of magnetite were observed to be dependent on the cross-linking density of the gel, and the heat generation of the nanoparticles was governed by their crystalline structure and particle size rather than solely the amount of formed iron oxide. [ABSTRACT FROM AUTHOR]

• Laccase was immobilized on organic-inorganic nanocomposite and applied to chlorophenol removal. • Immobilized laccase showed high enzyme loading, activity retention and storage stability. • Immobilized laccase exhibited excellent efficiency and reusability for 2,4-DCP removal. • The active conformation of immobilized laccase was retained efficiently. In this study, organic-inorganic nanocomposite including mesoporous silica SBA-15 and chitosan was combined using carboxyl-functionalized ionic liquid as the bridging agent (SBA-CIL-CS), and which was characterized by scanning electron microscope, Fourier transform infrared spectroscopy, thermogravimetric analysis, and nitrogen adsorption-desorption isotherms. Thus prepared nanocomposite was applied to laccase immobilization via physical adsorption (SBA-CIL-CS-Lac) and utilized in 2,4-dichlorophenol (2,4-DCP) removal for the first time. SBA-CIL-CS-Lac showed relatively high immobilization efficiency, activity retention (75.3%), pH stability and storage stability. Kinetic experiment showed SBA-CIL-CS-Lac had the eminent affinity to the substrate. Circular dichroism and fluorescence analysis verified the active conformation of SBA-CIL-CS-Lac was maintained well to keep its enzymatic activity. Compared with the previous methods, SBA-CIL-CS-Lac exhibited prominent catalytic efficiency and reusability as well as pH and temperature stability for 2,4-DCP removal. The removal rate of SBA-CIL-CS-Lac for 2,4-DCP could be up to ˜90% after 35 h. Moreover, 58.8% removal rate could be retained after five operation runs. These results indicated that organic-inorganic nanocomposite SBA-CIL-CS was an ideal support for enzyme immobilization. [ABSTRACT FROM AUTHOR]

• HNT-reinforced chitosan/PVA nanofibers were developed for skin tissue regeneration. • Presence of 3 and 5% HNT greatly improved the mechanical properties of nanofibers. • Swelling ratio of the chitosan/PVA nanofibers was doubled by incorporation of HNT. • Addition of HNT increased the biocompatibility of the nanofibers. • Glyoxal was introduced as a biocompatible crosslinker for chitosan/PVA nanofibers. In this study, in situ glyoxal crosslinked chitosan/poly (vinyl alcohol) (PVA) hydrogel nanofibers reinforced with halloysite nanotubes (HNT) were prepared by the electrospinning method without needing post-treatment for stabilization of the nanofibers in aqueous media. FTIR spectroscopy approved the formation of acetal bonds between glyoxal and hydroxyl groups of PVA and chitosan. Morphological studies by SEM/EDX and TEM in accordance with XRD patterns proved that HNT was successfully incorporated into the crosslinked chitosan/PVA nanofibers. The crosslinked nanofibers were insoluble in water. Due to the hydrophilic nature of HNT, the swelling of the nanofibers was increased from 272% for crosslinked chitosan/PVA nanofibers to around 400% for the HNT reinforced nanocomposite nanofibers. Comparing to chitosan/PVA nanofibers, the tensile strength of the crosslinked nanocomposite nanofibers was increased to 2.4 and 3.5 fold by incorporation of 3 and 5% HNT, respectively. Presence of HNT in chitosan/PVA nanofibers reduced the contact angle with water and increased the hydrophilicity of HNT-reinforced nanofibers favoring the attachment of fibroblast cells. Cytotoxicity studies by AlamarBlue assay showed that presence of HNT increased the biocompatibility of the nanofibers. It was also concluded that glyoxal can be used safely for crosslinking of chitosan/PVA nanofibers without any cytotoxic effect for fibroblast cells. From the results of this work, HNT reinforced chitosan/PVA nanofibers crosslinked by glyoxal are introduced as promising nanomaterials for skin tissue regeneration. [ABSTRACT FROM AUTHOR]

• Monodispersed chitosan nanospheres functionalized by mesoporous SiO 2 and folic acid were prepared. • The products have high drug loading efficiency, excellent circulation stability and sustained release property. • The products were pH-responsive, folic acid-triggered uptake and nuclear targeting. Ideal nanoscale drug delivery system (DDS) should be biocompatible, having targeted recognition and controlled release properties. In this work, monodispersed, doxorubicin (Dox) loaded chitosan (Cts) nanospheres functionalized by mesoporous SiO 2 and folic acid (FA) were prepared, briefly named as DCSF NSs. The prepared raspberry-like DCSF NSs had an average size of 440 nm and drug loading efficiency (DLE) of 42.61%. The drug release results confirmed that the release of Dox could be controlled by pH change. Cell apoptosis results indicated that the obtained DCSF NSs could kill 90% of MCF-7 cells in 48 h. Confocal laser scanning microscopy (CLSM) results further revealed that folic acid could mediate the cellular uptake of DCSF NSs. These results demonstrated that the obtained DCSF NSs were pH-responsive, folic acid-triggered nuclear targeted, which can be used as ideal DDS for tumor chemotherapy. [ABSTRACT FROM AUTHOR]

• The antibacterial photoactivity of curcumin loaded nanoparticles was investigated. • Nanoparticle ζ-potential significantly influenced their antibacterial phototoxicity. • Chitosan modified nanoparticles exhibited enhanced photoactivity against E. coli. • Substantial morphological changes of the irradiated bacteria were observed. The constant increase in multi-resistant bacterial strains and the decline in the number of newly approved antibiotics necessitate the development of alternative approaches to antibiotic treatment. In this study, a modern alternative approach to antibiotic therapy using photosensitiser encapsulated polymeric nanoparticles is presented. Cationic nanoparticles were prepared using a biodegradable and biocompatible polymer poly (lactic- co -glycolic acid), a stabiliser poly (vinyl alcohol) and chitosan. Dynamic light scattering and laser Doppler anemometry were used to determine particle size distribution and ζ-potential respectively. To quantify the antibacterial photodynamic effect of the nanoparticles, in vitro studies were performed using Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha to represent both a gram-positive as well as a gram-negative strain. It was demonstrated that the particle ζ-potential significantly influenced the antibacterial phototoxicity, gaining up to 3 log 10 higher efficacy for chitosan coated nanoparticles. Furthermore, neither irradiation alone nor curcumin in absence of light led to a significant growth reduction, confirming the photodynamic effect of curcumin. Electron microscopy has been used to study the morphological characteristics of the nanoparticles as well as their interaction with bacteria and the changes of bacterial morphology and ultrastructure upon photodynamic treatment. An increased adherence of the chitosan modified nanoparticles to the bacteria and structural damage upon photodynamic treatment was clearly evident and confirmed the results from in vitro studies. [ABSTRACT FROM AUTHOR]

• Hybrid scaffolds were prepared by biomimetic mineralization on natural and synthetic polymers. • The scaffolds improved the mineralization capacity and the well distribution of crystals in the SBF. • The scaffolds with interconnected microstructures showed excellent mechanical, biocompatible and bioactive properties. To mimic the mineral component and the microstructure of natural bone, nanohydroxyapatite (nHAP)/polymer (natural and synthetic materials) composite scaffolds with micropore structures and good mechanical performance were prepared via the assistance of sonication and amidation. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed the biomimetic homogeneous formation of nHAP in the polymer matrix. Fourier transform infrared spectroscopy (FTIR) indicated that the polymer matrix regulated the crystallization of nHAP. The integration of synthetic/natural polymers benefited nHAP crystallization in the polymer matrix and thus improved the mechanical performance of the chitosan (CS)/collagen (Col)/ poly (lactic acid) (PLA)/nHAP scaffolds. The in vitro bioactivity ability was investigated by incubating in a simulated body fluid (SBF). The methyl thiazolyl tetrazolium (MTT) test, the acridine orange/ethidium bromide (AO/EB) and Giemsa staining showed that the scaffolds had good biocompatibility and could maintain the cell growth. Therefore, the CS/Col/PLA/nHAP scaffold is promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

• Chitosan based drug delivery system have opened up new avenues for treatment of periodontitits. • Chitosan based nanosystems hold immense promise in improving periodontal drug delivery. • Nanoparticles by the virtue of their size have the propensity to penetrate affected areas. • Excellent biodegradability of chitosan are a major attribute in nanoparticulate system. • Chitosan nanosystem controlled drug release, good retention around the periodontal pocket. Periodontal diseases are chronic infectious diseases and are a major oral health burden. With the progress in the understanding of etiology, epidemiology and pathogenesis of periodontal diseases coupled with the understanding of the polymicrobial synergy in the dysbiotic oral microbial flora, several new therapeutic targets have been identified. The strategies to curb bacterial growth and production of factors that gradually destroy the tissue surrounding and supporting the teeth have been the cornerstone for inhibiting periodontitis. Systemic administration of antibiotics for the treatment of periodontitis have shown several drawbacks including: inadequate antibiotic concentration at the site of the periodontal pocket, a rapid decline of the plasma antibiotic concentration to sub-therapeutic levels, the development of microbial resistance due to sub-therapeutic drug levels and peak-plasma antibiotic concentrations which may be associated with various side effects. These obvious disadvantages have evoked an interest in the development of localized drug delivery systems that can provide an effective concentration of antibiotic at the periodontal site for the duration of the treatment with minimal side effects. A targeted sustained release device which could be inserted in the periodontal pocket and prolong the therapeutic levels at the site of action at a much lower dose is the need of the hour. Chitosan, a deacetylated derivative of chitin has attracted considerable attention owing to its special properties including antimicrobial efficacy, biodegradability, biocompatibility and non-toxicity. It also has the propensity to act as hydrating agent and display tissue healing and osteoinducting effect. The aim of this review is to shine a spotlight on the chitosan based devices developed for drug delivery application in the effective treatment of various periodontal disorders. The chitosan based carriers like fibers, films, sponge, microparticles, nanoparticles, gels that have been designed for sustained release of drug into the periodontal pocket are highlighted. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chitosan was developed using N -halamine antibacterial compounds. • The consequence of the N -halamine addition to CS films on its surface parameters. • Correlation between type of N -halamine and chitosan composite properties. • UV radiation effect on the N -halamine-containing chitosan films. Abstract Several hydantoin derivatives and their N -halamine analogues were examined by spectroscopic methods (IR, 1H-NMR, 13C-NMR), elemental analysis (content of C, H, N), thermogravimetry (TGA), antibacterial tests and experiments of stability in aqueous solution. This research allowed the structural, thermal and antibacterial characteristics of obtained compounds. It was found, the thermal stability of hydantoins depends on their chemical structure and decreases when N -halamine moieties were introduced. In next step, synthesized biocides were added to the chitosan films. The antibacterial properties of received films were proved. It was found that after modification, the thermal stability of CS films decreases in most cases. The surface properties of obtained chitosan films before and after UV irradiation were investigated by means of contact angle measurements allowing the calculation of surface free energy. The chemical and structural changes during UV irradiation were studied by FTIR spectroscopy and SEM microscopy. The results indicated that the introduction of biocides to the CS material contribute to the photooxidation process. The degradation mechanism of obtained materials was proposed. The materials studied in this work may be used in various biomedical applications due to their confirmed biological activity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • CA-NEs were obtained by an innovative spontaneous emulsification method. • CMC microgels were easily fabricated using a solvent exchange method. • CMC films were rapidly prepared by electrospraying CMC microgels. • CA-NEs@CMC films possessed satisfactory antioxidant and antibacterial activities. • CA-NEs@CMC films could prolong shelf life of bread samples. Abstract Carvacrol (CA) was firstly made into physically stable nanoemulsions using an innovative spontaneous emulsification method with carvacrol itself as oil phase without introducing other carrier oils. Self-crosslinking carboxymethyl chitosan (CMC) microgels via intermolecular hydrogen bonds were then fabricated using a simple solvent exchange method with ethanol as poor solvent. The CMC microgels obtained were rapidly deposited on the surface of tin foil using an electrospray technique to produce the CMC films. The stability of the films in water was further intensified by using Ca2+ as cross-linking agent. Also, the carvacrol nanoemulsions (CA-NEs) were loaded into the CMC films by utilizing swelling property of CMC microgels in aqueous solution. The results showed that the CA-NEs@CMC composite films possess satisfactory antioxidant activity, good antibacterial activity against S. aureus and E. coli , and excellent ability to extend the shelf life of wheat bread. We believe that the present strategies to prepare CA-NEs, CMC microgels and their composite films also apply to other types of essential oils and polymers, and the CA-NEs@CMC composite film is an excellent candidate for the active packaging. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chitosan/poly(NVCL- co -IA- co -EGDMA) microparticles with multi-response properties. • Chitosan as protective agent against undesirable colloidal destabilization. • Extended release of ketoprofen at pH 7.4 and 37 °C. Abstract In this paper, chitosan was used as protective agent for dual temperature-/pH-sensitive poly(N -vinylcaprolactam- co -itaconic acid- co -ethylene- glycol dimethacrylate)- based hydrogel nanoparticles (poly(NVCL- co -IA- co -EGDMA)) aiming avoid their undesirable colloidal destabilization at different conditions of body human tissues. Thus, poly(NVCL- co -IA- co -EGDMA) was embedded into chitosan and a new solid dispersion was prepared via spray-drying and ketoprofen was used as carrier. Two different sizes of hydrogel nanoparticles (120.6 nm and 185.9 nm) were evaluated and they exhibited a drug encapsulation efficiency of the 39.6% and 57.8%, respectively. The smaller nanoparticles showed to be faster for releasing of ketoprofen at pH 7.4 and 37 °C due to their larger surface area and higher swelling ability. Chitosan played a role of a secondary barrier for the ketoprofen diffusion, extending its release compared to hydrogel nanoparticles alone. Among two concentrations (40 wt% and 70 wt%) of hydrogel nanoparticles related to chitosan, the first one induced higher percentages of ketoprofen release: 74.2% against 64.6%. In addition, the interactions between chitosan matrix and poly(NVCL- co -IA- co -EGDMA) did not change the multi-responsive behavior of hydrogels, suggesting the chitosan was efficient for keeping integrity of nanoparticles hydrogels. Chitosan/poly(NVCL- co -IA- co -EGDMA) hybrid microparticles seems to be a promising new carrier for release of hydrophobic drugs, such as ketoprofen. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chitosan and carboxymethyl chitosan substrates were evaluated for ochratoxin A detection. • Competitive inhibition immunoassay was developed for the analysis of OTA in coffee. • Limit of detection on carboxymethyl chitosan substrate was lower as compare to chitosan. Abstract This study demonstrates the evaluation of ochratoxin A (OTA) in coffee on compact surface plasmon resonance (SPR) biosensors based on crosslinked chitosan and carboxymethyl chitosan nanomatrix substrates. Ochratoxin A is a toxic secondary metabolite widely produced by Aspergillus and Penicillium fungi and requires regular quantification and detection in food samples. The gold coated SPR chips were synthesized with chitosan and carboxymethyl chitosan through spin coating technique. The SPR nanomatrix chips were used for the immobilization of ochratoxin A-bovine serum albumin (OTA-BSA) conjugate to develop a competitive inhibition immunoassay. The monoclonal ochratoxin A antibodies (mAb-OTA) were used as biological receptors for the detection of OTA in buffer and coffee samples. The limit of detection (LOD) in coffee for chitosan (CS) and carboxymethyl chitosan (CMC) substrates was 5.7 ng/mL and 3.8 ng/mL, respectively. Compact surface plasmon resonance (SPR) system based on chitosan-based (CS-AU) nanomatrix substrates provides a platform for the detection of ochratoxin A with high sensitivity, accuracy, ease-of-use and cost-effectiveness. This compact SPR system can be used at farm and industrial levels for the detection of OTA in food matrices. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Miconazole nitrate was encapsulated within chitosan nanoparticles. • Average diameter of the nanoparticles ranging from 200 to 300 nm. • The nanoparticles were tested in vivo vulvovaginal candidiasis murine model. • The therapeutic efficacy was the same as a commercial cream formulation. Abstract Objectives In this study, polymeric nanoparticles based on chitosan incorporating the antifungal miconazole nitrate were fabricated and tested in vivo using murine vulvovaginal candidiasis. Methods Nanoparticles prepared by the ionotropic gelation method presented 200 to 300 nm diameter and polydispersity indexes ranging from 0.2 to 0.4. The nanoparticles were prepared to incorporate 63.9 mg/mL of miconazole nitrate to be tested in vivo. Murine vulvovaginal candidiasis was standardized using estradiol valerate before the animals were challenged by Candida albicans. Results The treatment using chitosan nanoparticles within miconazole nitrate presented the same therapeutic efficacy as miconazole nitrate in a commercial cream formulation, however using the antifungal content about seven-fold lower. This increase in the miconazole nitrate's therapeutic efficacy is may be due to the down-regulation of interleukin 10 (IL-10) expression. Conclusions Our data represent a proof of concept that can be exploited to achieve an alternative and promising therapy for the treatment of vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Fabrication of AgNPs-CS as a shell on a rigid PMMA core using heterocoagulation. • PMMA/AgNPs-CS coated SPNR films perform antibacterial action using dual mechanisms. • The presence of PMMA/AgNPs-CS on SPNR film suppresses cytotoxicity on fibroblasts. Abstract The antibacterial activity in sulphur prevulcanized natural rubber (SPNR) latex film was effectively improved by deposition of poly(methyl methacrylate) (PMMA) particles encircled with chitosan-coated silver nanoparticles (AgNPs-CS). With the focus on a green process, CS was selected as a safe reducing and stabilizing agent for the one-step synthesis of AgNPs-CS (38 nm, +40.4 mV) in an autoclave. The adsorption of small-sized AgNPs-CS directly onto rubber film did not provide an inhibitory effect on S. aureus. It also had a low antibacterial effect on E. coli. This is because of the particles becoming completely/partially submerged into the soft rubber matrix upon drying. Hence, the AgNPs-CS were fabricated as a shell surrounding a rigid PMMA core (496 nm, -30.9 mV). This was done using a heterocoagulation technique prior to coating on SPNR film. The presence of PMMA/AgNPs-CS on the surface of SPNR film effectively increased the surface roughness from ca. 44 to 150 nm. This substantially promoted the antibacterial activity against E. coli and S. aureus by way of contact killing and repelling mechanisms. The cytotoxicity on L-929 fibroblasts was also suppressed. This study would be, therefore, applicable to the development of antibacterial SPNR film with high surface roughness, low cytotoxicity. It could also be applied for other soft substrates. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chitosan-coated iron oxide nanoparticles were used as chlorhexidine (CHX) carriers. • A CHX-carrier nanosystem was successfully synthesized. • The nanosystem was effective against bacterial and fungal planktonic cells. • The nanosystem showed similar or superior antibiofilm effects compared to free CHX. Abstract This study synthesized and characterized a chlorhexidine (CHX)-carrier nanosystem based on iron oxide magnetic nanoparticles (IONPs) and chitosan (CS), and evaluated its antimicrobial effect on mono- and dual-species biofilms of Candida albicans and Streptococcus mutans. CHX was directly solubilized in CS-coated IONPs and maintained under magnetic stirring for obtaining the IONPs-CS-CHX nanosystem. Antimicrobial susceptibility testing for planktonic cells was performed by determining the minimum inhibitory concentration (MIC) of the nanosystem and controls. The effects of the IONPs-CS-CHX nanosystem on the formation of mono- and dual-species biofilms, as well as on pre-formed biofilms were assessed by quantification of total biomass, metabolic activity and colony-forming units. Data were analyzed by the Kruskal-Wallis' test or one-way analysis of variance, followed by the Student-Newman-Keuls' or Holm-Sidak's tests (α = 0.05), respectively. Physico-chemical results confirmed the formation of a nanosystem with a size smaller than 40 nm. The IONPs-CS-CHX nanosystem and free CHX showed similar MIC values for both species analyzed. In general, biofilm quantification assays revealed that the CHX nanosystem at 78 μg/mL promoted similar or superior antibiofilm effects compared to its counterpart at 39 μg/mL and free CHX at 78 μg/mL. These findings highlight the potential of CS-coated IONPs as preventive or therapeutic agents carrying CHX to fight biofilm-associated oral diseases. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Magnetic bioinspired hybrid scaffolds were prepared by in situ bionics strategy. • The Fe 3 O 4 particles and nHAP homogeneously nucleated into the matrix of CS/Col. • Scaffolds with micro/nanostructure possessed better biomineralized property. • Excellent biocompatibility and osteogenic potential were showed in this study. Abstract Magnetic-responsive materials are promising for applications in various biomedical fields. Especially, superparamagnetic nanoparticles are widely used in magnetic system for bone tissue engineering owing to superior biocompatibility and long term stability. Based on the idea of in situ bionics, we successfully incorporate the nano-hydroxyapatite (nHAP) and Fe 3 O 4 nanoparticles which were prepared by in situ crystallization and freeze-drying technique into the chitosan/collagen (CS/Col) organic matrix to achieve the uniform dispersion of inorganic substrate with nanometer-scale. The in vitro results of the physicochemical and biocompatibility tests showed that CS/Col/Fe 3 O 4 /nHAP magnetic scaffold possessed superior structural and mechanical performance for cell adhesion and proliferation, as well as the osteogenic differentiation. Mineralization experiments showed better bioactive and good ability of in situ biomimetic mineralization. Moreover, from the in vivo model of SD rats' skull defects proved that the CS/Col/Fe 3 O 4 /nHAP hybrid scaffold had a better tissue compatibility and higher bone regeneration ability when implanted into the skull defects comparing to control group. Herein, the magnetic hybrid micro/nanostructured scaffold showed a potential application for bone defect repair. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Structurally unrelated proteins can be encapsulated in chitosan-TPP nanoparticles. • Chitosan-TPP nanoparticles delivered proteins to mammalian cells. • Cellular uptake of chitosan-TPP nanoparticles was dependent on pH. Abstract We have successfully encapsulated two proteins, bovine serum albumin (BSA) and p53, in chitosan-tripolyphosphate (TPP) nanoparticles at various pH values from 5.5 to 6.5 and delivered the particles to human melanoma cells. The particles have diameters ranging from 180 nm to 280 nm and a zeta potential of +15 to + 40 mV. Cellular uptake of the particles by human skin melanoma cells was evaluated by: (i) fluorescence microscopy and (ii) gel electrophoresis showing that FITC-labeled BSA and p53 could be recovered in the soluble cell fraction after lysis of the cells. Our data also show that the highest cellular uptake takes place at the lowest pH as the particles have the highest positive charge under these conditions. The method we describe appears to be a general method for delivery of proteins to cells using chitosan-TPP nanoparticles as a drug delivery system, since structurally unrelated proteins such as BSA and p53 with different isoelectrical points can be encapsulated in the chitosan-TPP nanoparticles and be effectively internalized by the cells. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Amphiphilic quaternary ammonium chitosan (CS612) produced by an acid-free method. • CS612 has good biocompatibility and potent antimicrobial activity against microbes. • CS612 rapidly bound onto preformed bacterial and fungal biofilms. • CS612 eradiated adherent microorganisms living in biofilms. Abstract Formation of biofilms on solid surfaces is a long-standing challenge to multiple medical and health-related applications. Once formed, biofilms are very difficult to destroy, and microorganisms in biofilms are much more resistant to antimicrobial agents than their free-floating counterparts. The current antimicrobial agents/disinfectants often have low residence time on biofilms, leading to low antimicrobial effect on biofilm microorganisms. We designed and synthesized an amphiphilic quaternary ammonium chitosan (CS612) as biocompatible antimicrobial agents that bind onto preformed biofilms to kill adherent microorganisms. CS612 was synthesized through an external acid-free approach, and showed excellent concentration-dependent cytocompatibility toward mammalian cells. Antimicrobial functions of CS612 were confirmed by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests against Gram-positive bacteria, Gram-negative bacteria, and fungi. CS612 rapidly bound onto preformed bacterial and fungal biofilms, and killed adherent microorganisms living in the biofilms. The biofilm-binding kinetic parameters were determined, pointing to a new strategy to manage microorganisms in biofilms and their accompanying problems. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We prepared cefuroxime conjugated chitosan (CEF-con-CH) hydrogel. • We attained sustained release of cefuroxime by ester hydrolysis. • Hydrolyzed cefuroxime showed good antibacterial activity. • CEF-con-CH hydrogel exhibited excellent hemocompatibility and cytocompatibility. Abstract Hydrogels are excellent drug delivery systems for the treatment of chronic wound infections. However, the problem of high burst release still remains a challenge that needs to be tackled. In terms of antibiotic release from the hydrogels, as the drug payload depletes it could act as a substrate for bacterial seeding which can create a life-threatening condition. Therefore, to provide the sustained effect of an antibiotic at the localized site via hydrogel matrix, we prepared a chitosan (CS) hydrogel system in which cefuroxime (CEF) is covalently conjugated with chitosan polymer via an ester linkage. To prepare the cefuroxime conjugated chitosan hydrogel, the formulations were optimized using different concentrations of cefuroxime, 0% (CS/CEF_0), 5% (CS/CEF_5), 10% (CS/CEF_10) and 20% (CS/CEF_20) w/w of chitosan. Fourier Transform Infra-red Spectroscopy (FTIR) confirmed the conjugation of cefuroxime and chitosan. The drug release studies showed that the release of cefuroxime was higher in the phosphate buffer (pH 7.4) with esterase enzyme and alkaline medium (pH 10) compared to phosphate buffer (pH 7.4) alone. Hemolysis assay was performed to demonstrate the hemocompatibility of the prepared hydrogel samples. The cell viability study using the L929 fibroblast and MG63 osteosarcoma cell lines revealed that synthesized hydrogel is biocompatible. Furthermore, a potent antibacterial activity for the extended time period proved the biological efficacy of a hydrolyzed cefuroxime. Thus, CS/CEF_5, CS/CEF_10, and CS/CEF_20 hydrogels have a promising future in the treatment of chronic wound infections. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • PEG or dextran-grafted chitosans replace parent polymer in layer-by-layer films. • Copolymer–based films show high resistance to protein adsorption. • Antifouling properties of copolymer films are controlled by side chains overlapping. • PEG and dextran side chains are equally effective in preventing protein adsorption. Abstract Layer-by-layer (LbL) films with enhanced resistance to protein adsorption were obtained on the basis of N-grafted copolymers of chitosan with polyethylene glycol (PEG) or dextran (DEX). The copolymers with the backbone molecular weight of 18 and 450 kDa, side chains of PEG of 5.0 and 0.9 kDa, DEX of 6.0 kDa and the degree of amine groups substitution χ Sub as high as ∼0.25 were alternated with dextran sulfate (DS) to assemble up to 10 bilayer films. The film material contains 85±5% of water with virtually no effect of the copolymer structure. By utilizing the graft copolymers and applying suitable number of copolymer/DS bilayers to the surface, the mass of adsorbed fetal bovine serum proteins was decreased by 70–85% as compared to that on unmodified chitosan/DS film. In terms of overlapping side chains on the LbL surface the copolymers of PEG and DEX are equally effective in tailoring protein-resistant materials. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Developed synergistic trastuzumab decorated TPGS-g-chitosan nanoparticles for breast cancer therapy. • TPGS-g-chitosan was synthesized and confirmed by various spectroscopic techniques. • Cellular uptake, bioadhesive study on SK-BR-3 cells and cytotoxicity of nanoparticles were performed. • The in-vivo pharmacokinetic study showed enhancement in relative bioavailability of docetaxel. • Synergistic effect of TPGS-g-chitosan nanoparticles has improved the targeted drug delivery. Abstract Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted as well as targeted nanoparticles were in the range of 126–186 nm and 74–78% respectively. In-vitro studies on SK-BR-3 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional formulation i.e., Docel™. The IC 50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than Docel™. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than Docel™. Further, after i.v administration, non-targeted and targeted nanoparticles achieved 3.48 and 5.94 times prolonged half-life in comparison to Docel™. The area under the curve (AUC), relative bioavailability (F R) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles when compared to Docel™. The histopathology studies of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney when compared to Docel™. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Skilled preparation of positionally substituted quaternized chitin/chitosan. • Negligible antibacterial effect against E. coli of quaternized chitin maybe due to lower negative charge. • Antibacterial effect against S. aureus of quaternized chitin was derived from –NR 3 ＋. • High antibacterial effect against E. coli of quaternized chitosan was derived only from -NH 2. • Ultra high antibacterial effect against S. aureus of quaternized chitosan was derived both from -NH 2 and -NR 3 ＋. Abstract The positionally substituted 2′- O -hydroxypropyl trimethyl ammonium chloride chitin (2′- O -HTACCT) with different substitution degree of quaternary ammonium salt were synthesized directly from β -chitin, after that these 2′- O -HTACCT were then deacetylated to obtain corresponding 2′-O-hydroxypropyl trimethyl ammonium chloride chitosan (2′- O -HTACCS) with different deacetylation degree. The antibacterial activity and mechanism against E. coli and S. aureus of these 2′- O -HTACCT and 2′- O -HTACCS were investigated with various techniques. The results demonstrated that the 2′- O -HTACCT had antibacterial effect against S. aureus , but it had negligible antibacterial effect against E. coli, maybe due to the lack of anionic compound such as teichoic acid on the E. coli 's cell wall. Impressively, the high antibacterial effect against E. coli of the 2′- O -HTACCS was derived only from its -NH 2 , but the ultra high antibacterial effect against S. aureus of the 2′- O -HTACCS was derived both from its -NH 2 and -N+(CH 3) 3 , and enhanced as its pH value decreased. Thus, the positionally substituted 2′- O -HTACCS played an important role as a high-performance antibacterial bio-resource polymer against E. coli and S. aureus. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A facile mussel-inspired synthesis of the nanoagent with dual responsive property. • The nanoagent can kill bacteria in multiple ways without leading to cytotoxicity. • The nanoagent can be recycled and reused easily. • The nanoagent can serve as a novel candidate in wound disinfection. Abstract Antibiotics have been widely used in clinical applications to treat pathogenic infections at present, but the problem of drug-resistance associated with the abuse of antibiotics has become a large threat to human beings. Herein, we developed an antibacterial nanoagent by coating quaternized chitosan (QCS) on the surface of Fe 3 O 4 nanoparticles-anchored graphene oxide (GO), which enabled QCS and GO to achieve synergistic effects on killing the drug-resistant bacteria. Systematical antibacterial experiments showed that the prepared nanoagent had antibacterial ability, which was significantly enhanced after the introduction of near-infrared (NIR). Importantly, the nanoagent could be easily recycled and reused without the reduction of the antibacterial ability. During the test time, this nanoagent exhibited no obviously toxic side effect to cells. Given the above advantages, we anticipate that the nanoagent has a promising future in various applications such as wound disinfection, water purification, and surface sterilization of medical devices. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • HNTs surface was modified with Fe 3 O 4 , chitosan and 2-D calcium phosphate nanoflakes. • M-HNTs-CTs- CaP was characterized by FE SEM, FE HR-TEM, XPS, FT-IR and VSM. • M-HNTs-CTs- CaP gave very strong osteoconduction potential of hADMSCs. • Fe 3 O 4 , chitosan and CaP contributed synergistically for osteoconduction enhancement. • M-HNTs-CTs- CaP have a potential application in orthopaedic field. Abstract Halloysite nanotubes (HNTs) are known to be the highly emerging materials in nano-medicinal applications. However, comprehensive exploitation of HNTs for the regenerative medicinal applications is still necessary to be done. Therefore, towards enhancing the osteogenic potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs), this study synthesized a novel and multifunctional nanoscaffold of chitosan (CTs) functionalized supermagnetic halloysite nanotubes (M-HNTs) decorated with the calcium phosphate 2-D nanoflakes (CaP) (termed as; M-HNTs-CTs- CaP). Stepwise modified nanoscaffolds were characterized by FE-SEM, FE-SEM-EDS, FE-HR-TEM, XPS, FT-IR and VSM analyses. The hADMSCs osteogenic potential was confirmed by calcification (Alizarin Red S staining), phosphate quantification and immunocytochemistry. Nanoscaffolds; CaP , M-HNTs- CaP and M-HNTs-CTs- CaP were significantly enhanced and up-regulated osteogenic potential compared to the HNTs, M-HNTs, M-HNTs-CTs. Among the nanoscaffolds studied, M-HNTs-CTs- CaP exhibited highest osteogenesis, due to the enhanced CaP distribution on M-HNTs-CTs surface, and synergistic osteoconduction contributed from Fe 3 O 4 , chitosan and CaP. Moreover, immunocytochemistry analysis and morphologically observation showed well differentiated osteoblast on the M-HNTs-CTs- CaP surface. Therefore, M-HNTs-CTs- CaP found to have a strong osteogenic potential of hADMSCs, and might be serve as highly applicable, next generation nanoscaffold for bone tissue engineering application. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Heparin and chitosan were immobilized on the surface of alkali-treated titanium. • The immobilized surfaces exhibited excellent antithrombotic activities. • The immobilized surfaces exhibited excellent antibacterial activities. Abstract Biomaterial-related thrombus formation and bacterial infections are still the most common causes for the failure of medical devices. We report a facile and a highly efficient strategy to inhibit thrombosis and bacteria attachment, by immobilizing heparin (HA) and chitosan (CS) on titanium (Ti). Alkali-treatment was firstly performed on Ti to form nanoporous network structures containing hydroxyl radical (−OH), followed by immobilizing HA and CS on alkali-treated Ti in turn by layer-by-layer assembly. HA was immobilized on alkali-treated surface by covalent immobilization and CS was immobilized on heparinized surface by electrostatic bonding. The successful immobilization of both HA and CS on Ti was confirmed by analyses of scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and water contact angles. The antithrombotic activities of the immobilized surfaces were demonstrated by a reduction in protein absorption, blood clot mass and platelet adhesion. Additionally, the immobilized surfaces also exhibited excellent antibacterial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The modified surfaces on Ti was established as an effective and promising method to simultaneous improve the hemocompatibility and antibacterial performances of blood contact medical device. [ABSTRACT FROM AUTHOR]

Graphical abstract We here report a facile synthesis of chitosan shelled quantum dot (QD/fGC) that holds essential properties requisite for biological applications, such as excellent water solubility, colloidal stability, and low nonspecific adsorption as well as ease of functionalization. By conjugation with amines, the QD/fGC bioconjugates were further applied for fluorescent labeling of live cells. Highlights • Facile synthesis of chitosan shelled quantum dot for biological applications. • QD/fGC is about 6.03 ± 1.50 nm (N = 399) in diameter. • The functionalized QD/fGC presented recognition of cells in fluorescent imaging. Abstract We here report a facile synthesis of chitosan shelled quantum dot (QD/fGC) that holds essential properties requisite for biological applications, such as excellent water solubility, super colloidal stability, and low nonspecific adsorption as well as ease of functionalization. In this method, the amphiphilic glycol chitosan fragment (MW 1.0–1.7 kDa) was assembled on the top of CdSeS/ZnS nanocrystal through hydrophobic interaction in aqueous solution, without displacing the native coordinating ligands, which result in a higher quantum yield of about 0.26, 46% of the uncoated CdSeS/ZnS QDs in chloroform (0.57). In addition, the prepared QD/fGC composes an individual semiconductor core and presents an extremely small size of about 6.03 ± 1.50 nm (n = 399) in diameter. By conjugation with bioactive amines via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-based hydroxyl activation approach, the functionalized QD/fGC presented excellent recognition of specific cells in fluorescent imaging. Our work provides a new general method of chitosan modification of hydrophobic nanoparticles for biomedical applications. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • PEGylated MTO-PENPs were constructed with PGMC and TPGS, respectively. • Physicochemical properties of MTO-PENPs, MTO-CPENPs and MTO-TPENPs were compared. • Cytotoxicity of MTO-TPENPs on MCF-7 cells was stronger than that of MTO-CPENPs. • Both CPENPs and TPENPs showed in vitro and in vivo prolonged circulation effects. Abstract Poly (ethylene glycol) (PEG) and its derivatives are not only used to improve the stability of drug-loaded nanoparticles but also prolong their stay in blood for extended durations. We, hereby, report mitoxantrone loaded polyelectrolyte nanoparticles (MTO-PENPs) based on the hyaluronic acid (HA) and chitosan hydrochloride (HCS) complexed with amphiphilic PEG derivatives, carboxylated PEG (100) monostearate (PGMC, MTO-CPENPs) and D-tocopheryl PEG 1000 succinate (TPGS, MTO-TPENPs), to extend the in vivo circulation time. Maximum encapsulation efficiency (>95%) was observed at 40 mg/mL of PGMC or TPGS. TEM showed that PENPs preparations were spherical with an average diameter around 200 nm. Both MTO-CPENPs and MTO-TPENPs showed better stability than MTO-PENPs during storage at 4 °C, offered better control over the release of drug than simple PENPs, and showed pH-sensitivity with faster drug release in acidic conditions. MTO-CPENPs showed greater aversion from the protein adsorption and phagocytic uptake by macrophages but their cytotoxicity against the cancerous cells was poor of the all, and yet MTO-TPENPs showed good cytotoxicity against the MCF-7 cells. In the pharmacokinetic study, both MTO-CPENPs and MTO-TPENPs exhibited significant prolongation in blood circulation of drug compared to MTO-PENPs and MTO solution in rats after intravenous administration. However, MTO-TPENPs showed no statistically significant difference in plasma profile of MTO than the MTO-CPENPs. This indicates that there are underlying mechanisms that need to be explored to use the PEGylation in a way that could prolong stay of the nanoparticles in blood without compromising their interactions with target cells. [ABSTRACT FROM AUTHOR]