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In this study, gelation behavior and cytocompatibility of 2.5D chitosan hydrogels were investigated in the presence of TiO 2 , CeO 2 and TiO 2 -CeO 2 composite nanoparticles. Chemical co-precipitation method was used for nanoparticle synthesis and they were heat treated at 600 °C and 700 °C. Gelation of the chitosan solutions was carried out at 37 °C in the presence of glycerol phosphate and genipin as crosslinkers. The gelation time of chitosan was decreased by all of the nanoparticles whereas its elastic modulus was increased by nanoparticles addition. Chitosan solutions containing CeO 2 or TiO 2 -CeO 2 nanoparticles showed faster gel formation compared to chitosan solutions containing only TiO 2 nanoparticles. CeO 2 @700 °C nanoparticles decreased the gelation time by 46% and increased elastic modulus by 14%. Average pore diameter of the hydrogel decreased from 127 ± 62 μm to 77 ± 33 μm, water uptake decreased 21% and thermal stability increased in the presence of CeO 2 @700 °C nanoparticles compared to chitosan hydrogel. Cell viability results indicated that chitosan hydrogels with or without nanoparticles created 2.5D environment supporting cellular proliferation approximately 1.5 times more than TCPS due to their high porous surfaces. Immunofluorescence images were also supported cell viability results. Therefore, CeO 2 or TiO 2 -CeO 2 composite nanoparticles incorporated 2.5D chitosan hydrogels may be alternative tissue engineering materials with their fast gelation, ease of use, low cost, light transparency, and cytocompatibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We developed a miniature gas-liquid coaxial flow device using glass capillaries, aiming to produce sub-100-μm Ca-alginate microspheres. Depending on collecting distance and the flow rates of nitrogen gas and alginate solution, however, Ca-alginate microparticles of different shapes were obtained. Spherical, monodisperse microparticles (microspheres) could only be obtained at certain gas flow rates and within a corresponding range of collecting distance. The result suggests that, for particles of this size, the gas flow rate and collecting distance are crucial for the formation of the spherical shape. We evaluated, as an example of its applications, the microsphere as a drug carrier using acetaminophen as a model drug. Large (~150 μm) and small (~70 μm) drug-loaded microspheres were prepared using two respective devices. Specifically, the drug-loaded microspheres were complexed with chitosan of different molecular weights. The dependence of in vitro drug release on the microsphere size and the chitosan molecular weight was examined. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Alginic acid sodium salt (PubChem CID: 5102882); Chitosan (PubChem CID: 71853); Calcium chloride (PubChem CID: 5284359); Sodium chloride (PubChem CID: 5234); Acetaminophen (PubChem CID: 1983); Polydimethylsiloxane (PubChem CID: 24771); n-Octadecyltrimethoxysilane (PubChem CID: 76486)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biocompatible hydrogels were prepared by mixing aqueous-acidic solution of chitosan with alkali lignin, a major by-product of the paper producing industries, for the first time, by sustainable means. Electrostatic interactions between the phenoxide groups in lignin and the ammonium groups on the chitosan backbone were found to be responsible for the ionotropic cross-linking. These gels were non-toxic to Mesenchymal stem cells, in vitro, and to zebrafish up to 100 μg/ml, in vivo. In addition, these gels provided a conducive surface for cell attachment and proliferation, making it suitable for application as scaffolds in tissue engineering. In presence of the hydrogel, NIH 3T3 mouse fibroblast cells showed good cell migration characteristics suggesting that the gel might be suitable for wound healing application. The chitosan-alkali lignin gelation system was further capable of removing ferric ions from contaminated water by way of complexation and coagulation. Cross-linked films of chitosan and alkali lignin could also be prepared by simply immersing chitosan films into a solution of alkali lignin. Alkali lignin was observed to diffuse into the chitosan "crystal", forming electrostatic cross-links between the chitosan chains. The choice of lignin, in comparison to the other ionotropic cross-linkers for chitosan, makes the cross-linking system, inexpensive and sustainable., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Considering the health benefits of tocotrienols, continuous works have been done on the encapsulation and delivery of these compounds. In this study, we encapsulated tocotrienols in chitosan-alginate microcapsules and evaluated their release profile. Generally, these tocotrienols microcapsules (TM) displayed high thermal stability. When subjected to pH adjustments (pH 1-9), we observed that the release of tocotrienols was the highest (33.78 ± 0.18%) under basic conditions. The TM were also unstable against the effect of ionic strength, with a high release (70.73 ± 0.04%) of tocotrienols even at a low sodium chloride concentration (50 mM). As for the individual isomers, δ-tocotrienol was the most sensitive to pH and ionic strength. In contrast, β-/γ-tocotrienols were the most ionic-stable isomers but more responsive toward thermal treatment. Simulated gastrointestinal model showed that the chitosan-alginate-based TM could be used to retain tocotrienols in the gastric and subsequently release them in the intestines for possible absorption.

The gelling behaviors of thiolated chitosan (TCS) in alkaline condition were investigated. Thioglycolic acid was conjugated onto chitosan backbone through amide bond formation. The variations of thiol group content were monitored in presence of H2O2 or different pH values (pH 7.0, 8.0, 9.0) in dialysis mode. Different from the decreasing thiol group content upon time in acidic condition, increasing amount of thiol groups was detected in alkaline pH during 120 min dialysis attributed to alkaline hydrolysis of intra-molecular disulfide bonds. The extent of which was larger at higher pH values. Higher degree of thiolation, thiomer concentration or pH values promoted gelation of TCS. Entanglement and coagulation of chitosan molecule chains and re-arrangement of disulfide bonds acted closely and dynamically in the gelation process. Disulfide bonds, especially inter-molecular type, are formed by synergetic effects of thiol/disulfide interchange and thiol/thiol oxidation reactions. TCS coated vascular stent displayed wave-like microstructure of parallel ridges and grooves, which favored HUVECs adhesion and proliferation. The biocompatibility, peculiar morphology and thiol moieties of TCS as stent coating material appear application potential for vascular stent., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In medical and pharmaceutical applications, chitosan is used as a component of hydrogels-macromolecular networks swollen in water. Chemical hydrogels are formed by covalent links between the crosslinking reagents and amino functionalities of chitosan. To date, the most commonly used chitosan crosslinkers are dialdehydes, such as glutaraldehyde (GA). We have developed novel GA like crosslinkers with additional functional groups-dialdehyde derivatives of uridine (oUrd) and nucleotides (oUMP and oAMP)-leading to chitosan-based biomaterials with new properties. The process of chitosan crosslinking was investigated in details and compared to crosslinking with GA. The rates of crosslinking with oUMP, oAMP, and GA were essentially the same, though much higher than in the case of oUrd. The remarkable difference in the crosslinking properties of nucleoside and nucleotide dialdehydes can be clearly attributed to the presence of the phosphate group in nucleotides that participates in the gelation process through ionic interactions with the amino groups of chitosan. Using NMR spectroscopy, we have not observed the formation of aldimine bonds. It can be concluded that the real number of crosslinks needed to cause gelation of chitosan chains may be less than 1%.

The structural properties of medium molecular weight chitosan (CHT), whey protein isolate (WPI) and native wheat starch (WS) from low- to intermediate-solid single systems and composite matrices were investigated. Analysis involved monitoring the thermal behavior of these biopolymers during controlled heating from 25 up to 95 °C and subsequent cooling to 5 °C under small deformation dynamic oscillation in-shear and micro differential scanning calorimetry experiments. Further information regarding the molecular interactions of components and overall network morphology of the systems was revealed through subjecting thermally developed gels to large deformation compression testing, scanning electron microscopy and infrared spectroscopy. Our study found a significant change in the structure of WPI networks upon incorporation of CHT in preparations due to electrostatic forces developing between the two polymeric constituents. In the tertiary system, the presence of low levels of starch contributed to a reduction in the firmness of the gel matrix. However, at higher additions of the polysaccharide, a recovery in the stored energy of composite materials was apparent, as recorded in the thermomechanical protocol., (Copyright © 2015. Published by Elsevier Ltd.)

The selection of appropriate probiotic strains is vital for their successful inclusion in foods. These strains must withstand processing to reach consumers with ≥106 CFU/g, ensuring effective probiotic function. Achieving this in commercial products is challenging due to sensitivity to temperature during processing. In this work, Lactobacillus reuteri DSM 17938 was microencapsulated by ionic gelation (with alginate or pectin) followed by polymeric coating (with whey protein concentrate or chitosan). Then, such microcapsules were incorporated into a strawberry puree, which was subsequently dehydrated at three temperatures (40 °C, 45 °C, and 50 °C) by Refractance Window®. The ultimate aim was to demonstrate the efficacy of the proposed methods from a technological point of view. Kinetic curves of the probiotic's viability showed a high cell loading (>109 CFU/g). Additionally, an average encapsulation efficiency of 91% and a particle size of roughly 200 µm were found. A decrease in the viability of the microorganism was observed as drying temperature and time increased. As a demonstration of the above, in a particular case, drying at 45 °C and 50 °C, viable cells were found up to 165 min and 90 min, respectively; meanwhile, drying at 40 °C, viable cells were reported even after 240 min. The greatest viability preservation was achieved with Refractance Window® drying at 40 °C for 240 min when microcapsules coated with whey protein concentrate were incorporated into puree; this procedure showed great potential to produce dehydrated strawberry snacks with moisture (15%), water activity (aw < 0.6), and viability (≥106 CFU/g) suitable for functional foods. The membrane-stabilizing properties of whey protein concentrate could prevent cell damage. In contrast, probiotics in chitosan-coated capsules showed reduced viability, potentially due to antimicrobial properties and the formation of cracks. These findings signify a breakthrough in the production of dehydrated snacks with the addition of probiotics, addressing challenges in preserving the viability of these probiotics during processing; thus, opening the possibility for the development of a probiotic strawberry snack. [ABSTRACT FROM AUTHOR]

Polyvinylidene fluoride (PVDF) porous membrane was prepared by a two‐step method of surface gelation‐immersion precipitation phase inversion. Chitosan/acetic acid solution and glutaraldehyde aqueous solution were sequentially sprayed onto the surface of the PVDF solution film, with chitosan crosslinking and gelation occurring simultaneously on the film surface. The solution film was then immersed in a coagulation bath to obtain a modified PVDF porous membrane. The effect of the crosslinking time of chitosan and glutaraldehyde on the structure and properties of the PVDF porous membrane was discussed. The results showed that with the prolongation of crosslinking time, the surface structure of the membrane changed from a dense skin layer to a porous structure; the porosity and the mean pore size of the modified PVDF membranes increased first and then decreased, and the contact angle gradually decreased. When the crosslinking time extended to 15 min, the water flux of modified membrane (M153) reached a maximum value. BSA dynamic cyclic filtration experiment showed that the retention rate (R) of the modified membrane was significantly improved, compared to 68.3% retention rate of the blank membrane (M000), but the crosslinking time had little effect on the retention rates of the four modified membranes. The antifouling data showed that the flux recovery rate of the blank membrane was 73.0%, while the flux recovery rate of the modified membrane can reach as high as 84.40%, and the irreversible pollution rate of the blank membrane was 27.7%, while the irreversible pollution rate of the modified membrane reduced to 15.6%. These results indicated that, after surface chitosan crosslinking, the hydrophilicity and antifouling properties of PVDF membranes were improved. Practitioner Points: Modified PVDF membranes with crosslinking CS coating were prepared by a two‐step method of surface gelation‐immersion precipitation phase inversion.‐OH groups and ‐NH2 groups of CS coating improve the hydrophilicity and the antifouling property of modified PVDF membranes.Modified PVDF membranes had larger mean pore size and higher porosity than unmodified membrane.Flux recovery rates of the modified membranes were higher than that of unmodified membrane.Pollution degree, reversible pollution rate, and irreversible pollution rate of modified membranes were lower than those of unmodified membrane. [ABSTRACT FROM AUTHOR]

Background: Polymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration. Results: Chitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8–56.2 mV values, while the dialyzed samples led to smaller particle sizes (152–184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process. Conclusions: In Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis. [ABSTRACT FROM AUTHOR]

Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm's aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 μg/cm2 vs. 96.8 μg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen's Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs. [ABSTRACT FROM AUTHOR]

Enzymes are readily inactivated in harsh micro-environment due to changes in pH, temperature, and ionic strength. Developing suitable and feasible techniques for stabilizing enzymes in food sector is critical for preventing them from degradation. This review provides an overview on chitosan (CS)-based enzymes encapsulation techniques, enzyme release mechanisms, and their applications in food industry. The challenges and future prospects of CS-based enzymes encapsulation were also discussed. CS-based encapsulation techniques including ionotropic gelation, emulsification, spray drying, layer-by-layer self-assembly, hydrogels, and films have been studied to improve the encapsulation efficacy (EE), heat, acid and base stability of enzymes for their applications in food, agricultural, and medical industries. The smart delivery design, new delivery system development, and in vivo releasing mechanisms of enzymes using CS-based encapsulation techniques have also been evaluated in laboratory level studies. The CS-based encapsulation techniques in commercial products should be further improved for broadening their application fields. In conclusion, CS-based encapsulation techniques may provide a promising approach to improve EE and bioavailability of enzymes applied in food industry. Enzymes play a critical role in food industries but susceptible to inactivation. Chitosan-based materials could be used to maintain the enzyme activity. Releasing mechanisms of enzymes from encapsulators were outlined. Applications of encapsulated enzymes in food fields was discussed. [ABSTRACT FROM AUTHOR]

Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman's reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box–Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10−1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10−4 cm/min), RIS suspension (0.2005 × 10−4 cm/min), and a marketed preparation (0.3401 × 10−4 cm/min). [ABSTRACT FROM AUTHOR]

Context: The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. Objective: We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. Results: The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2–8 μg/mL to 8−128 μg/mL, respectively. Formulation at concentrations <64 μg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. Conclusions: The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells. [ABSTRACT FROM AUTHOR]

Polysaccharide/silica hybrid microcapsules were prepared using ionic gelation followed by spray-drying. Chitosan and alginate were used as biopolymer matrices, and in situ prepared silica was used as a structuring additive. The prepared microparticles were used in two very different applications: the encapsulation of hydrophilic molecules, and as a support for palladium nanoparticles used as catalysts for a model organic reaction, namely the reduction of p-nitrophenol by sodium borhydride. In the first application, erioglaucine disodium salt, taken as a model hydrophilic substance, was encapsulated in situ during the preparation of the microparticles. The results indicate that the presence of silica nanostructures, integrated within the polymer matrix, affect the morphology and the stability of the particles, retarding the release of the encapsulated substance. In the second application, chloropalladate was complexed on the surface of chitosan microparticles, and palladium(II) was subsequently reduced to palladium(0) to obtain heterogeneous catalysts with an excellent performance. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to investigate the preparation of patuletin-encapsulated chitosan nanoparticles (PT-CS-NPs) using the ionic gelation method, evaluate their potential as anticancer agents, and invent a new method of differential pulse voltammetric analysis for patuletin (PT). Methods. Computational studies were conducted to assess the affinity of PT for chitosan, confirming a promising interaction. PT-CS-NPs were synthesized based on the computational outputs, resulting in nanoparticles with an angular structure and an average size of 6.168 nm. The cytotoxicity of PT and PT-CS-NP was evaluated in breast and colon cancer cell lines, and selectivity indices were calculated to assess safety profiles. The electrochemical behavior of PT was also investigated using the Britton–Robinson buffer. Results. PT-CS-NP exhibited both potent cytotoxicity and a favorable safety profile, showing the most active and safest pattern of cytotoxicity among the tested compounds. The electrochemical oxidation of PT was observed at 0.531 V vs. Ag/AgCl at pH 4.0.0. The concentration of PT showed a linear relationship with the corresponding peak current over the range of 10.0 x 10 − 9 : 10.0 x 10 − 5 M M, with a minimum limit of detection of 3.4 × 10(−9)M. The proposed method successfully measured PT, with a relative standard deviation below 2%. Conclusion. The preparation of PT-CS-NP via the ionic gelation method resulted in angular nanoparticles with a promising anticancer activity and safety profiles. The electrochemical behavior of PT was characterized, and a reliable method for PT quantification was established. [ABSTRACT FROM AUTHOR]

Naturally occurring polysaccharide chitosan has been recognized as one of the bio-polymers that has extensively been utilized for the adsorption of the wide spectrum of heavy metals, oil, pesticides, dyes, etc. present in a smaller concentration from wastewaters. In this domain, the hybrid or composite hydrogel bead forms of chitosan (bio-matrix) are potentially more efficient and stronger than the parent version in bringing the effluents to their discharge standards. Various methods of gelation and crosslinking with suitable solvents are contributing toward tailoring and reinforcing hydrogel beads, thus making a rigid structure suitable for multi-cycle use before disposal. The mechanism of the adsorption by cross-linked hydrophilic chitosan hybrid gel is also studied in this paper to understand the role of surface-based active sites of bio-matrix and facilitate the exchange of ligands through them. [ABSTRACT FROM AUTHOR]

In this work, we obtained supramolecular gels in deep eutectic solvents (DES) from polysaccharides like chitosan and chitosan : cellulose composites. We thoroughly characterized our gels by determining the minimum gelation concentration, as well as their porosity and swelling. We also investigated their mechanical properties by rheology, and morphology by scanning electron measurements. These properties were mainly influenced by the number of hydrogen bond sites on the hydrogen bond donor, (HBD), while FTIR-ATR investigation suggested that, upon gelation, cholinium cations interpose between polysaccharide chains affecting interchain hydrogen bonding. Our gels also exhibited self-healing and load bearing ability and proved injectable. Subsequently, we evaluated antioxidant ability of the gels by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. We found that gelation of the DES reduces their radical scavenging ability, so we doped the gels with natural antioxidants like trans-ferulic acid (TA) and α-tocopherol (VE), finding that their high scavenging ability is fully preserved in the gel matrix. We then prepared films from one of the gels and evaluated their stability to sunlight and exposure to water, finding that the TA-doped film was the most resistant to UV-light, and retained its radical scavenging ability even after being exposed to significant amounts of water. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (CNPs) are known to have great utility in many fields (pharmaceutical, agricultural, food industry, wastewater treatment, etc.). In this study we aimed to synthesize sub-100 nm CNPs as a precursor of new biopolymer-based virus surrogates for water applications. We present a simple yet efficient synthesis procedure for obtaining high yield, monodisperse CNPs with size 68–77 nm. The CNPs were synthesized by ionic gelation using low molecular weight chitosan (deacetylation 75–85%) and tripolyphosphate as crosslinker, under rigorous homogenization to decrease size and increase uniformity, and purified by passing through 0.1 μm polyethersulfone syringe filters. The CNPs were characterized using dynamic light scattering, tunable resistive pulse sensing, and scanning electron microscopy. We demonstrate reproducibility of this method at two separate facilities. The effects of pH, ionic strength and three different purification methods on the size and polydispersity of CNP formation were examined. Larger CNPs (95–219) were produced under ionic strength and pH controls, and when purified using ultracentrifugation or size exclusion chromatography. Smaller CNPs (68–77 nm) were formulated using homogenization and filtration, and could readily interact with negatively charge proteins and DNA, making them an ideal precursor for the development of DNA-labelled, protein-coated virus surrogates for environmental water applications. [ABSTRACT FROM AUTHOR]

Chitosan‐based hydrogels are prepared via the formation of polypseudorotaxanes (PPR), by selectively threading α‐cyclodextrin (α‐CD) macrocycles onto polymeric chains, which, through the formation of microcrystalline domains, act as junction points for the network. Specifically, host–guest inclusion complexes are formed between α‐CD and PEGylated chitosan (PEG‐Ch), resulting in the formation of supramolecular gels. PEG‐grafted chitosan is obtained with a reaction yield of 79.8%, a high degree of grafting (50.9% GW) and water solubility (≈16 mg mL−1), as assessed by turbidimetry. A range of compositions for mixtures of PEG‐Ch solutions (0.2–0.8% w/w) and α‐CD solutions (2−12% w/w, or 0.04–0.2% mol) are studied. Regardless of PEG content, gels are not formed at low α‐CD concentrations (<4%). Dynamic rheology measurements reveal stiff gels (G' above 15k) and a narrow linear viscoelastic region, reflecting their brittleness. The highest elastic modulus is obtained for a hydrogel composition of 0.4% PEG‐Ch and 6% α‐CD. Steady‐state measurements, cycling between low and high shear rates, confirm the thixotropic nature of the gels, demonstrating their capacity to fully recover their mechanical properties after being exposed to high stress, making them good candidates to use as in‐situ gel‐forming materials for drug delivery to topical or parenteral sites. [ABSTRACT FROM AUTHOR]

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient's quality of life. To address this need, we developed reduction-responsive chitosan-based injectable hydrogels via the inverse electron demand Diels–Alder reaction between tetrazine groups of disulfide-based cross-linkers and norbornene groups of chitosan derivatives, which were applied to the controlled delivery of doxorubicin (DOX). The swelling ratio, gelation time (90–500 s), mechanical strength (G'~350–850 Pa), network morphology, and drug-loading efficiency (≥92%) of developed hydrogels were investigated. The in vitro release studies of the DOX-loaded hydrogels were performed at pH 7.4 and 5.0 with and without DTT (10 mM). The biocompatibility of pure hydrogel and the in vitro anticancer activity of DOX-loaded hydrogels were demonstrated via MTT assay on HEK-293 and HT-29 cancer cell lines, respectively. [ABSTRACT FROM AUTHOR]

Nanogel-forming polymers such as chitosan and alginic acid have a number of practical applications in the fields of drug delivery, food technology and agrotechnology as biocompatible, biodegradable polymers. Unlike bulk macrogel formation, which is followed by visually or easily detectable changes and physical parameters, such as viscosity or turbidity, the formation of nanogels is not followed by such changes and is therefore very difficult to track. The counterflow extrusion method (or analogues) enables gel nanoparticle formation for certain polymers, including chitosan and its derivatives. DLS or TEM, which are typically used for their characterization, only allow for the study of the already-formed nanoparticles. Alternatively, one might introduce a fluorescent dye into the gel-forming polymer, with the purpose of monitoring the effect of its microenvironment on the fluorescence spectra. But apparently, this approach does not provide a sufficiently specific signal, as the microenvironment may be affected by a big number of various factors (such as pH changes) including but not limited to gel formation per se. Here, we propose a new approach, based on the FRET effect, which we believe is much more specific and enables the elucidation of nanogel formation process in real time. Tryptophan-Pyrene is suggested as one of the donor–acceptor pairs, yielding the FRET effect when the two compounds are in close proximity to one another. We covalently attached Pyrene (the acceptor) to the chitosan (or PEG-chitosan) polymeric chain. The amount of introduced Pyrene was low enough to produce no significant effect on the properties of the resulting gel nanoparticles, but high enough to detect the FRET effect upon its interaction with Trp. When the Pyr-modified chitosan and Trp are both present in the solution, no FRET effect is observed. But as soon as the gel formation is initiated using the counterflow extrusion method, the FRET effect is easily detectable, manifested in a sharp increase in the fluorescence intensity of the pyrene acceptor and reflecting the gel formation process in real time. Apparently, the gel formation promotes the Trp-Pyr stacking interaction, which is deemed necessary for the FRET effect, and which does not occur in the solution. Further, we observed a similar FRET effect when the chitosan gel formation is a result of the covalent crosslinking of chitosan chains with genipin. Interestingly, using ovalbumin, having numerous Trp exposed on the protein surface instead of individual Trp yields a FRET effect similar to Trp. In all cases, we were able to detect the pH-, concentration- and temperature-dependent behaviors of the polymers as well as the kinetics of the gel formation for both nanogels and macrogels. These findings indicate a broad applicability of FRET-based analysis in biomedical practice, ranging from the optimization of gel formation to the encapsulation of therapeutic agents to food and biomedical technologies. [ABSTRACT FROM AUTHOR]

Hemorrhage control, especially noncompressible wound hemostasis, is a tremendous challenge in military injuries and other traumas worldwide. Here, a cryogelation strategy and subsequent solvent exchange are developed for the hydrogen bond‐induced self‐assembly of chitosan fibers and the production of fast expandable chitosan cryogel. Importantly, the ambient drying process facilitates the repeatable deformation performance of the shape‐memory cryogel with a response time of ≈1.7 s. Due to the capillary‐like structure of the cryogel and high hydrophilicity, rapid shape recovery is accompanied by 41 times water absorption ability. It is further demonstrated that chitosan cryogel is beneficial for in situ tissue regeneration by taking advantage of the biodegradability and biocompatibility of chitosan. Thus, chitosan cryogels prepared by this simple and benign method should have efficient hemostatic effect on noncompressible bleeding and severe fatal high‐pressure hemorrhage. [ABSTRACT FROM AUTHOR]

Herein, the authors synthesised chitosan nanoparticles (Cs NPs) as a resveratrol (RSV) carrier and evaluated their efficacy in stimulating apoptosis in MDA‐MB 231 cells. Blank (Cs NPs) and RSV‐ Cs NPs (RSV‐Cs NPs) were synthesised via ionic gelation and characterised by using fourier‐transform infrared spectroscopy (FTIR), Scanning electron microscope, dynamic light scattering/Zeta potential and RSV release. MDA‐MB 231 cells were treated with RSV, Cs NPs and RSV‐Cs NPs (24, 48, and 72 h), followed by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay. Cell toxicity was evaluated using lactate dehydrogenase assay, and real‐time polymerase chain reaction was performed to explore apoptosis induction. FTIR spectra confirmed the NPs via the formation of cross‐linking bonds. Cs and RSV‐Cs NPs sizes were about 75 and 198 nm with 14 and 24 mV zeta potentials. The RSV entrapment efficiency was 52.34 ± 0.16%, with an early rapid release followed by a sustained manner. Cs and RSV‐Cs NPs inhibited cell proliferation at lower concentrations and IC50 values. RSV‐Cs NPs had the most cytotoxic effect and stimulated intrinsic apoptotic pathway, indicated by increased Bcl‐2‐associated x (BAX), BAX/Bcl‐2 ratio, P53 expressions, reduced Bcl‐2 and upregulated caspases 3, 8 and 9. RSV‐Cs NPs have a great potential to suppress invasive breast cancer cell proliferation by targeting mitochondrial metabolism and inducing the intrinsic apoptotic pathway. [ABSTRACT FROM AUTHOR]

The thermoresponsive drug-loaded hydrogels have attracted widespread interest in the field of medical applications due to their ease of delivery to structurally complex tissue defects. However, drug-resistant infections remain a challenge, which has prompted the development of new non-antibiotic hydrogels. To this end, we prepared chitosan-methacrylate (CTSMA)/gelatin (GEL) thermoresponsive hydrogels and added natural phenolic compounds, including tannic acid, gallic acid, and pyrogallol, to improve the efficacy of hydrogels. This hybrid hydrogel imparted initial crosslinking at physiological temperature, followed by photocuring to further provide a mechanically robust structure. Rheological analysis, tensile strength, antibacterial activity against E. coli, S. aureus, P. gingivalis, and S. mutans, and L929 cytotoxicity were evaluated. The experimental results showed that the hybrid hydrogel with CTSMA/GEL ratio of 5/1 and tannic acid additive had a promising gelation temperature of about 37 °C. The presence of phenolic compounds not only significantly (p < 0.05) enhanced cell viability, but also increased the tensile strength of CTSMA/GEL hybrid hydrogels. Moreover, the hydrogel containing tannic acid revealed potent antibacterial efficacy against four microorganisms. It was concluded that the hybrid hydrogel containing tannic acid could be a potential composite material for medical applications. [ABSTRACT FROM AUTHOR]

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions. [ABSTRACT FROM AUTHOR]

Objectives: Rutin has been broadly applied for treating several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. This research aims to increase the solubility of rutin using cyclodextrin and to develop a temperature)triggered in situ gelling system for dermal application. Materials and Methods: The solubility of rutin was increased with sulfobutyl ether-β-cyclodextrin (SBE-β-CD). Rutin- SBE-β-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using differential scanning calorimetry and fourier transform infrared spectroscopy. In situ gel formulations were prepared with pluronic F127 (PF127), a thermosensitive polymer, and chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer. In situ gel characteristics such as pH, clarity, gelation temperature, and viscosity were determined. Results: When the solubility diagrams were examined, it was concluded that SBE-β-CD showed a linear increase, therefore, AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature, and the rheological behaviors, and one formulation was selected. It was observed that the formulations had a pH between 6-6.1, and their gelation temperature decreased with increasing PF127 that was between 20°C to 34°C. For the selected formulation (formulation E3), 0.5% rutin and rutin/SBE-β-CD were transferred to the in situ gelling system. Because of in vitro release studies, it was observed that the release of the rutin/SBE-β-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours. Conclusion: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of rutin and rutin/SBE-β-CD. [ABSTRACT FROM AUTHOR]

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Oxidized pectin/N-succinyl chitosan (OP/NSC) hydrogel containing graphene oxide (GO) was developed as a self-healing, injectable and conductive hydrogel. The OP/NSC/GO hydrogel showed rapid gelation and excellent injectability due to the hydrogen bonding between GO nanosheets and NSC and OP macromolecules and Schiff-based crosslinking by amino and aldehyde functional groups of polysaccharide derivatives. The hydrogel had the best overall performance when the GO content was adjusted to 6 (mg/mL). The healing and gelation time of the hydrogel was 10 min and 13 s, respectively. The hydrogel also showed adequate swelling ability, appropriate conductivity, and good mechanical characteristics. Hemolysis tests indicated that all prepared hydrogels were non-hemolytic materials. In addition, GOs-loaded hydrogels showed low toxicity to fibroblast cells (L929), thus indicating good biocompatibility. These findings demonstrated the hydrogel's potential as a conductive, injectable, self-healing hydrogel for biomedical applications, particularly in tissue engineering. [ABSTRACT FROM AUTHOR]

Natural polyelectrolyte complexes (PECs) have been the subject of interest for scientific research owing to their sustainable potential in a broad variety of advanced technologies. Herein, bio-based and environmental friendly polyelectrolyte complexes (PECs) of Chitosan (CS) and Quince seed gum (QSG) were formed and studied as a function of polyelectrolyte concentration (0.3 and 0.5% w/v) and CS:QSG ratio (1:3, 1:1 and 3:1). Zeta potential and rheological behavior confirmed the formation of the complexes. The maximum electrostatic interaction occurred at the mixing ratio of 1:1 at 0.3% w/v where the zeta potential was − 2.3 mV. All viscoelastic values showed high dependency on mixing ratio and QSG concentration below and above critical entanglement concentration of QSG (0.3% w/v). Immediate gelation and viscoelastic behavior improvement were observed by time and temperature sweep tests. Fourier transform infrared spectroscopy (FTIR) results showed that the inter-biopolymeric complexes were formed through the interaction of –NH3+ and –COO−, together with hydrogen bonding. All samples depicted lamellar porous interconnected microstructure (maximum BET surface area of 23.5 m2/g) and three-dimensional sponge-like macrostructure. Without any additional crosslinking, the PEC with higher QSG volume ratio (3:1) and higher concentration (0.5% w/v) exhibited higher Methylene Blue (MB) adsorption capacity (30.88 mg/g) and removal efficiency (77.2%) at practical pH 6.0 than zwitterionic Rhodamine B (RB) and anionic Methyl Orange (MO). The experimental data were in line with the pseudo-second-order (PSO) adsorption kinetic and the Freundlich isotherm model. The eco-friendly CS-QSG PECs can be acted as a promising adsorbent for multiple dye removal. [ABSTRACT FROM AUTHOR]

Excessive accumulation of free radicals is closely related to the occurrence and development of various neurodegenerative diseases. In this study, a novel protocatechuic acid grafted carboxymethyl chitosan with oxidized sodium alginate (PCA-g-CMCS/OSA) hydrogel was developed to maintain the oxidation-antioxidation balance activities. By optimizing the pH-soluble range (pH > 6.4) of CMCS, PCA was grafted onto CMCS skeleton via EDC/NHS, and then conjugated with aldehyde group of OSA to form Schiff's base hydrogel at physiological temperature. The gelation time can be adjusted rapidly within 1–3 min by controlling the content of OSA. The shaped hydrogel exhibited porous network structure with high porosity (>90 %), swelling ratio (2000–3000 %) and rheological property, which is beneficial to cell growth and proliferation. The conjugates preserved excellent DPPH and ABTS radicals scavenging abilities and adequate biodegradability within 5 weeks. Moreover, with the release of PCA monomer due to degradation of the PCA-g-CMCS/OSA, the hydrogel also exhibited excellent biocompatibility and protective effect on H 2 O 2 -induced oxidative damage in PC12 cells. These results suggested that the PCA-g-CMCS/OSA hydrogel would appear to be a more attractive candidate for potential biomedical applications such as antioxidant drug release and tissue engineering implant material. • A novel protocatechuic acid grafted carboxymethyl chitosan with oxidized sodium alginate (PCA-g-CMCS/OSA) hydrogel was developed through the Schiff's base reaction. • The pH-soluble range (pH > 6.4) of the prepared CMCS is critical for the formation of PCA-g-CMCS/OSA hydrogel. • The gelation time of PCA-g-CMCS/OSA hydrogel can be adjusted rapidly within 1–3 min by controlling the content of OSA. • The PCA-g-CMCS/OSA hydrogel showed excellent biocompatibility and protective effect on H 2 O 2 -induced oxidative damage in PC12 cells. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly on the molecular weight of the polymers. Moduli for coacervates were found significantly higher than those of individual HA and CHI physical gels. A remarkable 1.5-fold increase in moduli was noted when catechol-conjugated HA and CHI were used instead. This was attributed to the conversion of coacervates to chemical gels by oxidation of 3,4-dihydroxyphenylalanine (DOPA) groups in HA and CHI to di-DOPA crosslinks. These rheological results put HA/CHI coacervates in the category of strong candidates as injectable tissue scaffolds or medical adhesives. [ABSTRACT FROM AUTHOR]

Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors. [ABSTRACT FROM AUTHOR]

The increase in the production of melanin level inside the skin prompts a patient-inconvenient skin color disorder namely; melasma. This arouses the need to develop efficacious treatment modalities, among which are topical nano-delivery systems. This study aimed to formulate functionalized chitosan nanoparticles (CSNPs) in gel form for enhanced topical delivery of alpha-arbutin as a skin whitening agent to treat melasma. Ionic gelation method was employed to prepare a-arbutin-CSNPs utilizing a 24 full factorial design followed by In vitro, Ex vivo and clinical evaluation of the nano-dispersions and their gel forms. Results revealed that the obtained CSNPs were in the nanometer range with positive zeta potential, high entrapment efficiency, good stability characteristics and exhibited sustained release of a-arbutin over 24 h. Ex vivo deposition of CSNPs proved their superiority in accumulating the drug in deep skin layers with no transdermal delivery. DSC and FTIR studies revealed the successful amorphization of a-arbutin into the nanoparticulate system with no interaction between the drug and the carrier system. The comparative split-face clinical study revealed that a-arbutin loaded CSNPs hydrogels showed better therapeutic efficacy compared to the free drug hydrogel in melasma patients, as displayed by the decrease in: modified melasma area and severity index (mMASI) scores, epidermal melanin particle size surface area (MPSA) and the number of epidermal monoclonal mouse anti-melanoma antigen recognized by T cells-1 (MART-1) positive cells which proved that the aforementioned system is a promising modality for melasma treatment. [ABSTRACT FROM AUTHOR]

Nanogel-forming polymers such as chitosan and alginic acid have a number of practical applications in the fields of drug delivery, food technology and agrotechnology as biocompatible, biodegradable polymers. Unlike bulk macrogel formation, which is followed by visually or easily detectable changes and physical parameters, such as viscosity or turbidity, the formation of nanogels is not followed by such changes and is therefore very difficult to track. The counterflow extrusion method (or analogues) enables gel nanoparticle formation for certain polymers, including chitosan and its derivatives. DLS or TEM, which are typically used for their characterization, only allow for the study of the already-formed nanoparticles. Alternatively, one might introduce a fluorescent dye into the gel-forming polymer, with the purpose of monitoring the effect of its microenvironment on the fluorescence spectra. But apparently, this approach does not provide a sufficiently specific signal, as the microenvironment may be affected by a big number of various factors (such as pH changes) including but not limited to gel formation per se. Here, we propose a new approach, based on the FRET effect, which we believe is much more specific and enables the elucidation of nanogel formation process in real time. Tryptophan-Pyrene is suggested as one of the donor–acceptor pairs, yielding the FRET effect when the two compounds are in close proximity to one another. We covalently attached Pyrene (the acceptor) to the chitosan (or PEG-chitosan) polymeric chain. The amount of introduced Pyrene was low enough to produce no significant effect on the properties of the resulting gel nanoparticles, but high enough to detect the FRET effect upon its interaction with Trp. When the Pyr-modified chitosan and Trp are both present in the solution, no FRET effect is observed. But as soon as the gel formation is initiated using the counterflow extrusion method, the FRET effect is easily detectable, manifested in a sharp increase in the fluorescence intensity of the pyrene acceptor and reflecting the gel formation process in real time. Apparently, the gel formation promotes the Trp-Pyr stacking interaction, which is deemed necessary for the FRET effect, and which does not occur in the solution. Further, we observed a similar FRET effect when the chitosan gel formation is a result of the covalent crosslinking of chitosan chains with genipin. Interestingly, using ovalbumin, having numerous Trp exposed on the protein surface instead of individual Trp yields a FRET effect similar to Trp. In all cases, we were able to detect the pH-, concentration- and temperature-dependent behaviors of the polymers as well as the kinetics of the gel formation for both nanogels and macrogels. These findings indicate a broad applicability of FRET-based analysis in biomedical practice, ranging from the optimization of gel formation to the encapsulation of therapeutic agents to food and biomedical technologies.

Ionic gelation is among the simplest processes for the development of chitosan nanoparticles reported so far in the literature. Its one-shot synthesis process in conjunction with the mild reaction conditions required are among the main causes for its success. In this work, we sought to optimize a set of physical parameters associated with the ionic gelation process at two different pH values. Following that, the NPs' freeze-drying and long-term storage stability were assayed, and their biocompatibility with HaCat cells was evaluated. The results show that NPs were more homogenously produced at pH 5, and that at this pH value, it was possible to obtain a set of optimum production conditions. Furthermore, of the assayed parameters, TPP addition time and overall reaction time were the parameters which had a significant impact on the produced NPs. Nanoparticle freeze-drying led to particle aggregation, and, of the cryoprotectants, assayed mannitol at 10% (w/v) presented the best performance, as the NPs were stable to freeze-drying and maintained their size and charge in the long-term stability assay. Lastly, the chitosan NPs presented no toxicity towards the HaCat cell line. [ABSTRACT FROM AUTHOR]

Nano-chitosan can be produced from blood clams (Anadara granosa) because they contain 14-35% of chitin. The production of nano-chitosan can be conducted by a bottom-up process using sodium tripolyphosphate (Na-TPP). The aims of this study are to produce nanochitosan from blood clamshell and to study the factor affecting the particle size of nanochitosan such as the ratio of chitosan to Na-TPP solution (v/v) and rotation speed of the centrifuge. The research shows that The chitin content on blood clamshell is 25.42%. The yield of chitosan from chitin is about 80.92%. The degree of deacetylation of chitin from blood clamshell reaches 63.18%. The effect of the ratio of chitosan to Na-TPP solution (R) and the rotation speed of centrifuge (N) on the particle size of nano-chitosan can be expressed by equation dp = 0.12 (R)0.714 (N)0.99. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (CSNPs) can be widely used in the food, pharmaceutical, and cosmetic sectors due to their high performance, unique properties, and high surface area. In this research, CSNPs were produced by the ionic gelation method and using sodium tripolyphosphate (STPP) as an appropriate technique compared to the conventional methods. To evaluate the effects of various factors on the size, zeta potential (ZP), and optimal synthesis conditions, different concentrations of CS (1, 3, and 5 mg/mL), STPP (0.5, 0.75, and 1 mg/mL), and CS to STPP ratio (1:1, 3:1, and 5:1) were applied and optimized using the response surface methodology. The size of CSNPs was increased by using higher concentrations of CS, STPP, and CS/STPP ratios. The value of ZP was determined positive and it increased with increasing CS concentrations and CS/STPP ratios. ATR-FTIR spectra revealed interactions between CS and STPP. The DSC thermogram of CSNPs showed a double sharp endothermic peak at about 74.5 °C (ΔH = 122.00 J/g); further, the TGA thermograms indicated the total weight loss of STPP, CS, and CSNPs as nearly 3.30%, 63.60%, and 52.00%, respectively. The XRD data also revealed a greater chain alignment in the CSNPs. Optimized, the CSNPs can be used as promising carriers for bioactive compounds where they also act as efficient stabilizers in Pickering emulsions. [ABSTRACT FROM AUTHOR]

Four medicament delivery formulations based on 5-fluorouracil in a chitosan substantial matrix were realized in situ via 3,7-dimethyl-2,6-octadienal element hydrogelation. Representative samples of the final realized compounds were investigated from an analytic, constitutional, and morphological viewpoint via Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The SEM images of the formulations were investigated in concordance with fractal analysis, and the fractal dimensions and lacunarity were computed. The developed mathematical multifractal model is necessarily confirmed by the experimental measurements corresponding to the 5-fluorouracil release outside the chitosan-formed matrix. [ABSTRACT FROM AUTHOR]

Background: As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect. Methods: CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay. Results: Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively. Conclusion: The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP. [ABSTRACT FROM AUTHOR]

Endowing silk fibroin (SF) with the thermosensitivity of rapid in situ gelation remains a challenge in the field of silk fibroin‐based tissue engineering scaffolds and injectable soft tissue fillers. In this study, thermosensitive hydroxybutyl chitosan (HBC)/SF hybrid hydrogels are prepared by physical interaction between HBC and SF. In HBC/SF hybrid system, hydrophobic segments of HBC are aggregated to form microaggregates at physiological temperature, which induce hydrophobic segments of SF to aggregate to the microaggregates by hydrophobic interaction, thus achieving the sol–gel transformation of the two components jointly. The observations and tests of the gelation process show that HBC/SF hybrids with mass ratios of 95/5, 90/10, 85/15, 80/20, 75/25, and 70/30 can complete sol–gel transition rapidly within 5–8 min at 37 °C, and have the reversibility of sol–gel transition. CCK‐8 assay results reveal that the cytotoxicity of HBC hydrogel is effectively reduced by the introduction of SF component. Thermosensitive HBC/SF hybrids have the potential to be used as injectable tissue engineering scaffolds and soft tissue filler. [ABSTRACT FROM AUTHOR]

A novel biologically active nanocomposite glycerohydrogel based on two biocompatible precursors, silicon and iron glycerolates, was synthesized by the sol—gel method in the presence of chitosan (Ch). The composition and structural features of the gel were characterized by advanced analytical methods including transmission electron microscopy, X-ray diffraction, and atomic emission spectroscopy. It was shown that iron(iii) monoglycerolate undergoes partial hydrolysis under the gelation conditions and exists as a separate nanoscale phase along with the hydrolysis products in cells of the 3D Si-containing polymeric gel network. This network is formed as a result of incomplete hydrolysis of silicon glycerolates in excess glycerol followed by homo- and heterofunctional condensation of silanol groups with the formation of Si-O-Si units containing residual glyceroxy groups at the silicon atom. Chitosan forms numerous intermolecular bonds with the 3D gel network, accelerates the process of gelation, makes the gel morphostructure more ordered, and increases the stability of the gel. The Si-Fe-Ch-containing glycerohydrogel is nontoxic and possesses hemostatic and wound-healing activity, being a promising topical medication for medical and veterinary practice. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels based on chitosan play an important role in the field of tissue engineering and drug delivery system, with excellent properties such as biocompatible, biodegradable, and minimally invasive. In this work, a dual ionically crosslinked injectable hydrogel was composed of polyelectrolyte complex (PEC) and sodium hydrogen carbonate (SHC) as non-toxic gel agent. The PEC was prepared by ionic interaction between positively charged chitosan and negatively charged thermosensitive polymer poly(NIPAm-co-AMPS). The injectable hydrogel with rapid gelation was obtained by optimizing feed ratio, SHC amount, concentration, and temperature. The swelling, temperature sensitive, rheological, and cytotoxic properties of the hydrogels were evaluated. The potential of hydrogels applied in drug delivery system was studied by measuring the release property in vitro, taking aspirin as drug model. The results showed that the hydrogel exhibited a sol–gel transition at about 37 ℃, when the volume ratio of CS (20 mg/mL), PNAM (4.0 mg/mL), and SHC (0.4 M) was 1:0.2:0.5; the hydrogel with good mechanical strength and gelation time of 1–3 min in the physiological conditions was obtained. The hydrogels prepared with high SHC concentration or more gel agents showed shorter gelation time and better thermostability. The hydrogel presented a 1-day sustained release of aspirin with no significant burst release in vitro. The release properties demonstrated that the hydrogels released aspirin in a sustained manner, about 87% in 24 h. L929 cells had good survival and proliferative rates within CS-PNAM/SHC hydrogel after 24 h, showing excellent biocompatibility. Therefore, the injectable thermos-responsive hydrogels formed by CS-PNAM/SHC and loaded with aspirin turned into a smart drug delivery system, showing great potential for controlled release. [ABSTRACT FROM AUTHOR]

The stiffness and gelation temperature of thermo-responsive chitosan (CS), glycerophosphate (GP) hydrogel is not enough for differentiation of BMSCs and injecting use in bone defect repair. To improve these weaknesses, a kind of injectable hydrogel (PMCG) was prepared with Chitosan (CS), glycerophosphate (GP), polygonatum polysaccharide modified montmorillonite (PMMT). The gelation temperature of CS/GP (CG) hydrogel was 42 °C, the maximum mechanical strength was 1061 Pa. with the amount of PMMT increased, the gelation temperature decreased to 28 °C, and the maximum stiffness increased to 6789 Pa. At the same time, with the addition of PMMT, the swelling property of hydrogel was improved. The cytocompatibility of PMCG decreased than CG which maybe result from the poor cytocompatibility of montmorillonite, but it was improved with increasing amount of PMMT, which indicated the cell proliferation promoting effect coming from polygonatum polysaccharide. The SEM-EDX exhibited that these hydrogels possessed excellent morphological characteristics and could promote mineralization in simulated body fluid (SBF) solution, PMCG-2 Ca/P has a Ca/P ratio of 1.63 ± 0.04, which is similar to the ratio of human bone mineral (Ca/P ratio of 1.55–1.75). The cell viability confirmed the application availability of the hydrogel. In light of the effect on osteoblasts maturation promoting effect and decrease of osteoclast of polygonatum polysaccharide. We come to the conclusion that it is an effective strategy to improve the mechanic strength and gelation temperature, and keep the osteogenesis promoting effect at the same time. [ABSTRACT FROM AUTHOR]

Therapeutic macromolecules (e.g., protein and peptide drugs) present bioavailability challenges via extravascular administration. The nasal route presents an alternative non-invasive route for these drugs, although low bioavailability remains challenging. Co-administration of permeation enhancers is a promising formulation approach to improve the delivery of poorly bioavailable drugs. The aim of this study was to prepare and characterize chitosan microparticulate formulations containing a macromolecular model compound (fluorescein isothiocyanate dextran 4400, FD-4) and a bioenhancer (piperine). Ionic gelation was used to produce chitosan microparticle delivery systems with two distinct microparticle sizes, differing one order of magnitude in size (±20 µm and ±200 µm). These two microparticle delivery systems were formulated into thermosensitive gels and their drug delivery performance was evaluated across ovine nasal epithelial tissues. Dissolution studies revealed a biphasic release pattern. Rheometry results demonstrated a sol-to-gel transition of the thermosensitive gel formulation at a temperature of 34 °C. The microparticles incorporating piperine showed a 1.2-fold increase in FD-4 delivery across the excised ovine nasal epithelial tissues as compared to microparticles without piperine. This study therefore contributed to advancements in ionic gelation methods for the formulation of particulate systems to enhance macromolecular nasal drug delivery. [ABSTRACT FROM AUTHOR]

The CS-TPP nanoparticles were synthesized and their efficiency for removal of arsenic (V) ions at the optimum conditions was investigated. The optimum conditions for CS-TPP nanoparticles were obtained with the mass ratio of tripolyphosphate to chitosan of 1: 2 and pH = 5.0. The experimental data for the adsorption of As (V) ions followed the Freundlich adsorption isotherm and the maximum adsorption capacity was 77 mg/g at pH = 6.0. All isotherm experiments were performed at room temperature (25 °C). The crosslinking of sodium tripolyphosphate with the chitosan led to a decrease in crystallinity of the formed particles which then resulted in an improvement in metal ion sorption properties. [ABSTRACT FROM AUTHOR]

Wide application of chitosan in modern technologies is limited by the lack of reliable and low-cost techniques to prepare size-tuned constructs with a complex surface morphology, improved optical and mechanical properties. We report a new simple method for preparation of transparent thermoreversible chitosan alcogels from chitosan/H 2 O/ethanol ternary systems. This method, termed "low temperature thermally induced phase separation under non-freezing conditions" (LT-TIPS-NF), fine tunes gelation by adjusting only temperature (from 5 to −25 °C) and varying the initial content of chitosan (from 0.5 to 2.0 wt%) and ethanol (from 28.5 to 47.5 vol%). Transparent non-swelling final constructs of complex shape are prepared by fixing the pre-formed alcogels with a base solution. The size of the gel constructs is limited only by the dimensions of the mold and the cooling chamber. The LT-TIPS-NF is applicable both in injection molding and 3D printing techniques. The in vitro and in vivo experiments show the absence of prominent cytotoxicity and well-defined cell adhesion on the obtained hydrogels. Thus, this facile and scalable technique provides the multifunctional chitosan gel preparation with easily controlled properties exploiting inexpensive, renewable, and environmentally friendly source polysaccharide. These materials have prospects for a variety of uses, especially for biomedical applications. [Display omitted] • An approach for thermoreversible chitosan-based alcogel formation by LT-TIPS-NF method was developed. • Nanofibrous hydrogels with high transparency and increased mechanical strength were fabricated by fixation of alcogels. • Molding and 3D-printing of hydrogel constructs with complex structure morphology was performed. • The prepared hydrogels demonstrated good cell viability in vitro and high biocompatibility in vivo. [ABSTRACT FROM AUTHOR]

This review focuses on the modification of chitosan and gelatin-based hydrogel composite polymers for wound healing. First, the mechanical properties of several nanocomposite polymer hydrogels are compared based on water content, tensile strength, toughness and tensile strain. Furthermore, key findings on several modification techniques of the mechanical properties of chitosan are summarized. For example, we show that complexation of iron ions improves mechanical properties better than most other metal ions. Subsequently, gelatin – based hydrogel polymeric systems are compared on the basis of their preparative techniques, time to hemostasis, in vivo model and wound type, blood loss in treatment groups, biocompatibility and adhesive strength. Next, major outcomes on several techniques for improving the mechanical properties of gelatin biopolymer for wound healing are discussed. Then, effects of crosslinking on mechanical properties and hydrogel biocompatibility, in particular, the relationship between DHT crosslinking and gelation concentration are presented. Finally, research on adhesive anti-biofilm hydrogels are summarized, with focus on bacterial cellulosic, and chitosan – based hydrogels. Though similar reviews have been presented, the role of specific biological macromolecule-based composites such as chitosan and gelatin, have not been reviewed for some time despite the abundance of primary research findings. Knowledge gap and a list of unaddressed research questions are presented to aid further work in the field. [ABSTRACT FROM AUTHOR]

Myocardial infarction is a major cause of death worldwide and remains a social and healthcare burden. Injectable hydrogels with the ability to locally deliver drugs or cells to the damaged area can revolutionize the treatment of heart diseases. Herein, we formulate a thermo-responsive and injectable hydrogel based on conjugated chitosan/poloxamers for cardiac repair. To tailor the mechanical properties and electrical signal transmission, gold nanoparticles (AuNPs) with an average diameter of 50 nm were physically bonded to oxidized bacterial nanocellulose fibers (OBC) and added to the thermosensitive hydrogel at the ratio of 1% w/v. The prepared hydrogels have a porous structure with open pore channels in the range of 50–200 µm. Shear rate sweep measurements demonstrate a reversible phase transition from sol to gel with increasing temperature and a gelation time of 5 min. The hydrogels show a shear-thinning behavior with a shear modulus ranging from 1 to 12 kPa dependent on gold concentration. Electrical conductivity studies reveal that the conductance of the polymer matrix is 6 × 10−2 S/m at 75 mM Au. In vitro cytocompatibility assays by H9C2 cells show high biocompatibility (cell viability of >90% after 72 h incubation) with good cell adhesion. In conclusion, the developed nanocomposite hydrogel has great potential for use as an injectable biomaterial for cardiac tissue regeneration. [ABSTRACT FROM AUTHOR]