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DNA may be the most versatile molecule discovered to date. Beyond its well-known central role in genetics, DNA has the potential to be a remarkably usefultechnological material. It has been demonstrated as a scaffold for the assemblyof organic and inorganic nanomaterials [1]; a vehicle for drug delivery [2]; amedium for computation [3]; and a possible wire for transporting electricalsignals [4]. A key factor in exploiting DNA in these ways is the ability tointegrate DNA with other materials. In this paper, we review two approachesto forming DNA complexes with functional nanomaterials: (1) linking DNAwith single-wall carbon nanotubes (SWCNTs), which can then be used asnanoscale electrical contacts for probing electron transport in DNA; and (2)directed nanoassembly of Au nanoparticles using DNA/PNA (peptide nucleicacid) hybrid scaffolds.

In the treatment of acute lymphoblastic leukemia, 6-mercaptopurine (6-MP) is commonly used. Yet, short half-life in plasma, poor water solubility, severe side effects and variable bioavailability limit its use. GSH-responsive prodrugs (3&5) and biotin receptor targeted were made to enhance the intracellular accumulation related to 6-MP in the cancer cell. In compound 5, nanoparticles (NPs) have been prepared through conjugating 6-MP to carbon dots (nanocarriers) through GSH-sensitive carbonyl vinyl sulfide linkage, and surface decoration with biotin. Compound 3 was synthesized by direct conjugation of 6-MP to the biotin through GSH-sensitive linkage. In-vitro drug release study of NPs showed good stability in the phosphate buffer saline (PBS), which contains 100 µM GSH at (pH 7.40). Yet, the cumulative rate of the drug release that is associated with samples that contain the GSH medium of 10 mM reached 79.6% in acetate buffer at (pH 5.8). In vitro cytotoxicity study (MTT assay) demonstrated that compound 3 showed higher inhibition ratios on biotin receptor overexpressed cell lines (MCF-7, HepG2) and lower cytotoxicity on normal cell lines (CHO). Compound 5 showed good activity, comparable to 6-MP against (MCF-7, HepG2), and much lower cytotoxicity on (CHO).

The majority of formulations available so far are used in oral forms despite of several pharmaceutical challenges, as this route is the most convenient way of drug delivery. Equally, it necessitates the required need of dose optimization for reduced toxic effects and dosing frequency. Therefore, in this study, we have conceptualized the fabrication of gastro-retentive microspheres of Tinidazole by using a variable drug and ethyl cellulose ratios that will enhance its gastric absorption, retention time along with the sustained pharmacological activity. The scanning electron microscopy and micrometrical studies exhibited their smooth, spherical surface with the particle size range of 244–294 µm. Further, they were floated successfully on the fluid due to their low bulk density and provided the sustained release in simulated gastric fluid, suggesting their suitable gastro-retentive behavior in-vivo. Thus, the prepared formulation proved to be a better gastro-retentive drug delivery system with sustained release, thereby reducing dosing frequency and side effects.

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH- and H2O2-responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch, has been developed to achieve self-regulated administration. The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] (PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H2O2 and pH stimuli due to the chemical change of H2O2 sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase (GOx, which can oxidize glucose to gluconic acid and in-situ produce H2O2) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

Introduction: The plant used in the present study is Cassia fistula, which belongs to the family Leguminosae and has been used in traditional medicinal systems due to the presence of a copious amount of Phytochemicals with various properties. Aims: This study is focused on the extraction of phytochemicals from the Cassia fistula flower and its subsequent encapsulation into chitosan matrix for applications in drug delivery. Chitosan is approved by FDA for its use in Pharmaceutical industries. Methods: As described by several analytical techniques such as FT-IR, NMR, Thermal analysis, and SEM, the microsphere thus prepared by the current study is predicted to release the desired extract with medicinal properties in a controlled manner, allowing for more convenient and desired levels of drug administration. The swelling study and release study of the prepared microsphere have been carried out in physiological pH 2 and 7.4. NMR study has shown that sitosterol and friedelin have been encapsulated successfully into the chitosan matrix. Results: The microspheres have shown up to 80% swelling in pH 2 upto 8 days, and 60% of the in- -vitro controlled drug release has also been found in pH 2 upto 2 days. The thermal studies using TGA and DSC supported the thermal stabilities of CS beads, CFFE and CFFE-CS beads, Also, it showed the dispersion of the CFFE in the cavities of the Chitosan matrix. Conclusion: The Biomedical application of the synthesized CFFE-CS beads has also been reported on the basis of their antibacterial studies.

Introduction Temporomandibular-joint osteoarthritis (TMJOA) management is a major challenge. Minimally invasive therapies (based mainly on injections) have been developed to increase local efficacy and limit adverse systemic effects. However, the requirement for repeat injections due to a short duration of action and expensive healthcare costs have pushed researchers to develop, via tissue engineering, drug-delivery systems (DDSs). In this literature systematic review, we aim to provide an overview of studies that tested DDSs on a TMJOA model. Material and methods We searched on PubMed for articles published from November 1965 to March 2021 on DDSs using a TMJOA model. We highlighted the different DDSs and the active molecule employed. Route of drug administration, model type, test duration, and efficacy duration were assessed. To evaluate the quality of each study, a protocol bias was tested using QUADAS-2™. Results Of the 10 studies that were full text-screened, four used a poly(lactic-co-glycolic acid)-based delivery system. The other DDSs employed chitosan-based hydrogels, microneedles patches, nanostructured lipid carriers, or poloxamer micelles. Hyaluronic acid, nonsteroidal anti-inflammatory drugs, and analgesics were used as active molecules in five studies. The main way to administer DDSs was intra-articular injection and the most used model was the rat. Discussion Various DDSs and active molecules have been studied on a TMJOA model that could aid TMJOA management. Further works using longer test durations are necessary to validate these advances.

Aims and objectives: In this study, an attempt was made to synthesize, characterize, and develop many applications of functionalized rare metal oxide nanoparticles. Herein, a new strategy for drug delivery is developed to functionalize magnetite nanoparticles to improve their performances in the delivery of celecoxib. Materials and methods: Magnetite Fe3O4@SiO2 nanoparticles are synthesized by the sol-gel method. The surface of the hydroxyl groups was extended by treating with cerium nitrate salt; finally, sodium hydroxide was anchored to the surface hydroxyl groups to produce cerium oxidefunctionalized Fe3O4@SiO2@CeO2 magnetic nanoparticles (FSC). The synthesized sample was characterized by FT-IR, FESEM, VSM, TGA, and XRD. Afterward, the functionalized nanoparticles were examined in the delivery of celecoxib as an active drug model involving cerium oxide and hydroxyl functional groups. Results: For this purpose, the amount of loading/release of the drug was investigated in different amounts of nanocomposite and pH values. Conclusion: The results of the present investigation indicate that the formulations (mFSC=5 mg, pH=3.3) can be considered as best among various formulations with respect to particle size, entrapment efficiency, and in-vitro successful drug release.

Recently, multifunctional nanoparticles have shown great prospects in cancer treatment, which have the ability to simultaneously deliver the drug, image and target tumor cells. In this paper, we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate (HA-FCNs/ACP) with multifunctional properties for drug delivery, bio-imaging, and targeting treatment. HA-FCNs/ACP shows an ability to load curcumin (Cur) with pH-sensitive responsive drug release behavior and excellent biocompatibility. HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells (A549 cells). Meanwhile, the viability of A549 cells was significantly inhibited in vitro. The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells Hence, the as-prepared nanoparticles have promising applications in treating tumor disease.

Calix [4] arene refers to a group of large cyclic compounds involving a sequence of phenols, which are obtained through the hydroxylation reaction process of phenol and aldehyde derivatives. Calixarenes have a rigid and three-dimensional structure. Nanoparticles can be used in drug delivery due to their ability to enter cells. The application of a carrier for drug delivery is very effective on improving their performance. In order to employ calixarene nanoparticles as the carriers of mercaptopurine drug, their ability and type of adsorption were examined on laboratory scale. In this study, by examining the temperature changes on the course of adsorption and by matching the data against Langmuir adsorption isotherm, Freundlich, and Dubin Radushkovich, the numbers of all thermodynamic constants of this process were calculated. The obtained adsorption capacities indicated that the elevation of the initial concentration leads to the enhanced adsorption capacity. Moreover, by considering the obtained thermodynamic constants, it was found that the adsorption process is exothermic, while the values of Gibbs free energy ∆G0 and the adsorption energy Ea showed that the adsorption process was spontaneous and chemical.

Nanotechnology is considered one of the emerging fields of science that has influenced di-verse applications, including food, biomedicine, and cosmetics. The production and usage of materials with nanoscale dimensions like nanoparticles are attractive parts of nanotechnology. Among different nanoparticles, zinc phosphate nanoparticles have attracted attention due to their biocompatibility, bi-osafety, non-toxicity, and environmental compatibility. These nanoparticles could be employed in vari-ous applications like anticorrosion, antibacterial, dental cement, glass ceramics, tissue engineering, and drug delivery. A variety of physical, chemical, and green synthesis methods have been used to synthe-size zinc phosphate nanoparticles. All these methods have some limitations along with certain ad-vantages. Chemical approaches may cause health risks and environmental problems due to the toxicity of hazardous chemicals used in these techniques. Moreover, physical methods require high amounts of energy as well as expensive instruments. However, biological methods are free of chemical contami-nants and eco-friendly. This review is aimed to explore different methods for the synthesis of zinc phosphate nanoparticles, including physical, chemical, and more recently, biological approaches (using various sources such as plants, algae, and microorganisms). Also, it summarizes the practicable applica-tions of zinc phosphate nanoparticles as anticorrosion pigment, dental cement, and drug delivery agents.

Diflapolin is a dual FLAP/sEH inhibitor with potent anti-inflammatory efficiency in cellular assays and experimental in vivo studies. Despite these outstanding characteristics, its high lipophilicity and plasma protein binding hamper the bioactivity in blood. To overcome these limitations, diflapolin was encapsulated in poly(lactic-co-glycolic acid) nanoparticles to develop an efficient and biocompatible drug delivery system. Two different cosolvent approaches were tested showing the possibility to exchange dimethyl sulfoxide in the organic phase by the sustainable 400 g/mol poly(ethylene glycol). A particle size of 220 nm and the amorphous encapsulation of diflapolin in high amounts rendered the nanoparticles appropriate for the intended application. Excellent biocompatibility of the nanoparticles was demonstrated in an ex ovo hen's egg model. The potent suppression of FLAP-dependent 5-lipoxygenase product formation by the nanoparticles in human whole blood, superior to the free drug, makes them to a promising drug delivery system to improve the bioactivity of diflapolin.

Background: Synthetic polymers present disadvantages such as high cost, limited availability, safety concerns, environmental hazards and overtime accumulation in body. Lignin, an aromatic biopolymer, is highly abundant and offers various advantages including cost effectiveness, biocompatibility and biodegradability. It also possesses various pharmacological activities including antioxidant, antibacterial, anticancer and UV protection, thus lignin has become a popular biopolymer in recent years and is no more considered as bio-waste rather an extensive research is been carried out on developing it as drug carrier. Lignin also has non-biomedical applications including dispersing agents, surfactants, detergent/cleaning agents, energy storage, etc. Methods: This review compiles patents granted on production of technical lignin, different lignin therapeutic carriers and its biomedical and non-biomedical applications. The literature is collected from recent years including both articles as well as patents and is carefully analyzed and compiled in an easy to comprehend pattern for guiding future research. Results: The reviewed patents and articles highlighted the advancement made in lignin isolation and valorization. Numerous lignin nanoformulations as drug delivery agents or as standalone entities with various pharmacological actions like antibacterial, antioxidant or UV protectant have been reported. As well as industrial applications of lignin as adhesives, insulators or supercapacitors have also made lignin a biopolymer of choice. Conclusion: Lignin being a bio-inspired polymer has huge potential in commercial applications. New methods of lignin isolation from lignocellulosic biomass including physical pretreatments, solvent fraction, and chemical and biological pretreatment have been widely patented. Several micro/nano lignin formulations with improved and controllable reactivity like nanocontainers, nanocapsules, nanoparticles have also been reported recently. Also various pharmacological properties of lignin have also been explored, thus valorization of lignin is a hot topic of hour.

Poly (ethylene glycol)-poly (n-butyl cyanoacrylate) (PEG-PBCA) is a remarkable drug delivery carrier for permeating blood-brain barrier. In this work, a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA. A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than 1.1. Furthermore, the reaction time reduced 60% compared to conventional stirred tank reactor process. Chemical structures of as-prepared polymers were characterized. In vitro drug delivery performance was evaluated. The cytotoxicity of PEG-PBCA to brain microvessel endothelial cells (BMVEC) decreases with the extension of the PEG chain and the shortening of the PBCA chain. The polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG block. Results of blood-brain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation, while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride (Dox). The average apparent permeability coefficient increased 1.7 and 0.25 times than that of raw Nile red and Dox, respectively. High-gravity intensified condensation polymerization should have great potential in brain drug delivery system.

Systemic chemotherapy has lost its position to treat cancer over the past years mainly due to drug resistance, side effects, and limited survival ratio. Among a plethora of local drug delivery systems to solve this issue, the combinatorial strategy of chemo-hyperthermia has recently received attention. Herein we developed a magneto-thermal nanocarrier consisted of superparamagnetic iron oxide nanoparticles (SPIONs) coated by a blend formulation of a three-block copolymer Pluronic F127 and F68 on the oleic acid (OA) in which Curcumin as a natural and chemical anti-cancer agent was loaded. The subsequent nanocarrier SPION@OA-F127/F68-Cur was designed with a controlled gelation temperature of the shell, which could consequently control the release of curcumin. The release was systematically studied as a function of temperature and pH, via response surface methodology (RSM). The bone tumor killing efficacy of the released curcumin from the carrier in combination with the hyperthermia was studied on MG-63 osteosarcoma cells through Alamar blue assay, live-dead staining and apoptosis caspase 3/7 activation kit. It was found that the shrinkage of the F127/F68 layer stimulated by elevated temperature in an alternative magnetic field caused the curcumin release. Although the maximum release concentration and cell death took place at 45 °C, treatment at 41 °C was chosen as the optimum condition due to considerable cell apoptosis and lower side effects of mild hyperthermia. The cell metabolic activity results confirmed the synergistic effects of curcumin and hyperthermia in killing MG-63 osteosarcoma cells., Graphical abstract Image 1, Highlights • A magneto-thermal nanocarrier was developed to deliver anti-cancer drug of curcumin. • The curcumin release profile was modelled as a function of temperature and pH, using Response Surface Methodology. • In-vitro studies on MG-63 osteosarcoma cell line showed a synergistic effect of temperature and curcumin at 41 °C. • The optimum condition of the alternative magnetic field was reported to provide 41 °C stably.

Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery. However, most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements. In the present study, we prepared a semi-interpenetrating network composite gel (CG) by incorporating short chain chitosan (CS) into a covalent tetra-armed poly(ethylene glycol) network. In addition to satisfying physicochemical, mechanics, biocompatibility, and cell affinity requirements, this CG easily encapsulated acetylsalicylic acid (ASA) via electrostatic interactions and chain entanglement, achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell (PDLSC) proliferation and osteogenic differentiation. In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model. This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1, which upregulated M2 macrophage recruitment and polarization in situ, indicating its appealing potential in bone tissue engineering., Graphical abstract Image 1, Highlights • A facile method to prepare the composite gels with advantages of easy operation, good biocompatibility and biodegradability. • Composite gels can simultaneously fulfill the mechanical strength and cell-compatibility requirements. • Composite gels can achieve the loading and sustained release of acetylsalicylic acid via electrostatic interaction and chain entanglement. • Acetylsalicylic-acid-encapsulated composite gel is paramount to promote PDLSCs-mediated bone regeneration. • The underlying mechanism might be associated with upregulation of MCP-1 and macrophage M2 polarization.

A mitochondrial electron transport chain member complex I inhibitor, amobarbital, can reduce oxidative damage and chondrocyte death, eventually preventing post-traumatic osteoarthritis (PTOA). Viscosupplementation using a crosslinked hyaluronic acid (HA) hydrogel is currently applied clinically for knee OA pain relief. In this work, we utilized the HA hydrogel as a drug delivery vehicle to improve the long-term efficacy of amobarbital. Here we evaluated the pharmaceutic stability of amobarbital when dispersed in a crosslinked HA hydrogel formulated in proportions intended for clinical use. We validated a high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) method following International Conference for Harmonization Q2(R1) guidelines to ensure its suitability for amobarbital detection. The feasibility of this formulation's drug delivery capability was proven by measuring the release, solubility, and drug uniformity. The amobarbital/HA hydrogel showed comparable amobarbital stability in different biological fluids compared to amobarbital solution. In addition, the amobarbital/HA hydrogel imparted significantly greater drug stability when stored at 70°C for 24 hours. In conclusion, we confirmed the pharmaceutical stability of the amobarbital/HA hydrogel in various conditions and biological fluids using a validated HPLC-UV method. This data provides essential evidence in support of the use of this amobarbital/HA formulation in future clinical trials for PTOA treatment.

Carfilzomib (CFZ) is an FDA-approved proteasome inhibitor with antineoplastic properties against various cancers, yet its short blood retention time after intravenous injection (< 30 min) makes clinical applications limited to multiple myeloma. We previously developed ternary polypeptide nanoparticles (tPNPs) as a new nanoparticle formulation of CFZ to overcome these limitations. The formulation was prepared by polyion complexation between poly(ethylene glycol)-poly(L-glutamate) block copolymers (PEG-PLE) and CFZ-cyclodextrin (CD) inclusion complexes, where CDs were positively charged with 7 primary amines attached while PEG-PLE carried 100 carboxyl groups per polymer chain. Although tPNPs greatly improved biostability of CFZ, CFZ-loaded tPNPs (CFZ-tPNPs) still showed burst drug release and mediocre drug retention under physiological conditions. To address these issues, organic acids are tested as stabilizers in this study to improve particle stability and drug retention for tPNPs. Charge densities in the core of CFZ-tPNPs were optimized with selected organic acids such as citric acid (CA) and lactic acid (LA) at varying mixing ratios. Organic acids successfully maintained small particle size suitable for intravenous injection and drug delivery (diameters < 60 nm), improved CFZ solubility (> 1 mg/mL), allowed for lyophilization and easy reconstitution in various buffers, enhanced drug retention (> 60% post 24 h incubation), and suppressed burst drug release in the first 6 h following solubilization. These results demonstrate that organic acid stabilized tPNPs are useful as an injection formulation of CFZ, which may expand the utility of the proteasome inhibitor.

Purpose:The Optilume® Drug Coated Balloon (DCB) is a urethral dilation balloon with a paclitaxel coating that combines mechanical dilation for immediate symptomatic relief with local drug delivery ...

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.

Background: Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the Blood-Brain Barrier (BBB) impedes the delivery of curcumin to the brain, limiting its therapeutic potential. Objective/Aim: This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the bloodbrain barrier. Methods: The data for the compilation of this review work were searched in PubMed Scopus, Google Scholar, and Science Direct. Result: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.

The therapy of non-small lung cancer (NSCLC) is limited by wide metastasis and chemotherapy resistance, herein, we present a new cancer-targeting prodrug PBG with the integration of real-time fluorescence visualization. The potent anticancer drug Gefitinib conjugates a biotin recognition ligand yielding the prodrug PBG via a GSH-activatable disulfide bond linker. Once coupling a near-infrared azo-BODIPY fluorophore into the molecular structure of PBG, we obtain its fluorescent theranostic TBG. The prodrug PBG can sustain Gefitinib release by the high level of GSH in the pathophysiological milieu. We evaluate the drug delivery of the prodrug PBG using fluorescent TBG in PC9 cancer bearing nude mice models, which indicate that TBG can be utilized to monitor the in vivo drug release process. Prodrug PBG can be targeted to accumulate in the cancer lesion with a better and efficaciously therapeutic result compared with the single Gefitinib treatment in cells and in vivo. The fluorescence images also reveal that the targeting accumulation and longitudinal retention of anticancer drug in cancer lesions will contribute to the superior therapeutic effects. The above applications of our new prodrug PBG and its fluorescent theranostic TBG have the potential contribution to the research in biology and the clinical medicine.

Background: using a combination of chemotherapeutic agents with novel drug delivery platforms to enhance the anticancer efficacy of the drug and minimizing the side effects, is imperative to lung cancer treatments. Objective: The aim of the present study was to develop, characterize, and optimize porous poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles for simultaneous delivery of docetaxel (DTX) and celecoxib (CXB) through the pulmonary route for lung cancer. Methods: Drug-loaded porous microparticles were prepared by an emulsion solvent evaporation method. The impact of various processing and formulation variables including PLGA amount, dichloromethane volume, homogenization speed, polyvinyl alcohol volume, and concentration, was assessed based on entrapment efficiency, mean release time, particle size, mass median aerodynamic diameter, fine particle fraction, and geometric standard deviation using a twolevel factorial design. An optimized formulation was prepared and evaluated in terms of size and morphology using a scanning electron microscope. Results: FTIR, DSC, and XRD analyses confirmed drug entrapment and revealed no drug-polymer chemical interaction. Cytotoxicity of DTX along with CXB against A549 cells was significantly enhanced compared to DTX and CXB alone and the combination of DTX and CXB showed the greatest synergistic effect at a 1/500 ratio. Conclusion: In conclusion, the results of the present study suggest that encapsulation of DTX and CXB in porous PLGA microspheres with desirable features is feasible and their pulmonary co-administration would be a promising strategy for the effective and less toxic treatment of various lung cancers.

An extensive data set has been developed and used to further the progress of a model-informed design of controlled drug release. An improved drug-release model with mechanistic modeling of hydrolytic polymer degradation is used and validated by comparing model predictions to in vitro experiments. Combining parameter estimates from the literature with model fits to the data set, this study can aid in achieving a priori design of controlled drug release from a model PLGA release system. A systematic series of model release systems were formulated with FITC-labeled dextran, as a surrogate for biopharmaceuticals, in PLGA rods over a broad range of compositions. While general comparisons between the model and experiments were favorable, important discrepancies were identified for several formulations with significant first-phase drug release. Supported by cross-sectional fluorescence microscopy images of the FITC-dextran distribution within the rods, this first-phase release was attributed to a combination of two main factors: (1) percolation of the drug particles and (2) swelling of and pore formation in the rods due to water uptake. These observations indicate the importance of careful selection of the PLGA polymer grade when designing drug release systems but also reflect a need for better understanding of phenomena such as pore formation. Adapting model parameters, without modifying the physical processes included in the model, enabled accurate fitting of the experimental data for all formulations, highlighting the applicability of the model.

Cancer is one of the major reasons for mortality across the globe. Many side-effects are associated with the formulations available in the market, affecting the quality of life of the patients. This has caused the researchers to find an alternative source of medications, such as herbal medicine, showing a promising effect in anticancer treatment; one such source is Pomegranate, which belongs to the family Punicaceae. Punica granatum contains many polyphenols that have antioxidant, antidiabetic, and therapeutic effects in the treatment and management of metabolic and cardiovascular diseases, as well as a favourable effect on anticancer therapy. Polyphenols like punicalin, punicalagin, and ellagic acid are a few of the many compounds responsible for the anticancer activity of pomegranate. Many preparations of pomegranate, such as Pomegranate Juice (PJ), Pomegranate seed oil (PSO), Pomegranate peel extract (PoPx), etc. are used in various clinical studies. These polyphenols show anticancer activity by either arresting the cell cycle in the G2/M phase, inducing apoptosis or damaging the DNA of tumor cells. This review explicitly discusses the role and mechanism of bioactives obtained from the pomegranate in the treatment and management of cancer. The chemical structure, properties, and role of pomegranate in the treatment of breast, lung, thyroid, colon, and prostate cancer have been focused on in detail. This review also discusses various targeted drug delivery approaches for tumour treatment as well as patented preparation of pomegranate compounds along with the ongoing clinical trials.

Mitochondria are appealing targets in cancer therapy for providing a suitable microenvironment and energy supply. Herein, we constructed a glycosylated poly(amido amine)/celastrol (PAMAM/Cel) complex for hypoxia-activated mitochondria-specific drug delivery and chemothermal therapy to inhibit tumor growth and metastasis. The complex was characterized by high photothermal conversion efficiency, hypoxia-sensitive polyethylene glycol (PEG) outer layer detachment, and alkaline-sensitive drug release. The complex showed specific cellular uptake in glucose transporter 1 (GLUT1)-overexpressing tumor cells and mitochondrial accumulation in a hypoxic environment. Combined with near-infrared (NIR) laser irradiation, the complex exhibited higher cytotoxicity, apoptosis induction, and metastasis inhibition rates due to the synergistic chemothermal effect. Similarly, the complex also targeted tumors and accumulated in mitochondria in tumor-bearing nude mice, resulting in superior inhibitory effects on tumor growth and metastasis as well as low systematic toxicity. Further mechanistic studies discovered that the complex impaired the mitochondrial membrane, reduced adenosine triphosphate (ATP) content, and regulated metastasis-related protein expression. Thus, the present study provides a promising nanomedicine for tumor therapy.

The objective of the present study was formulation and evaluation of pulsatile release tablets of Atenolol. A tablet system consisting of cores which was coated with layers of swelling and rupturable coatings. Cores containing Atenolol as model drug were prepared by direct compression with appropriate ratios of lactose and microcrystalline cellulose and then coated sequentially with different ratios of an inner swelling layer containing HPMC and an outer rupturable layer of Ethyl Cellulose. The effect of level of swelling layer and rupturable coating was investigated. The different formulation press coated by using different weight ratios of Hydroxy Propyl Methyl Cellulose (HPMC) / Ethyl Cellulose (EC) / both HPMC and EC. The optimum result was achieved in formulation containing HPMC: EC weight ratios. The F3 batch achieved a highest burst release after the lag time which is applicable pulsatile drug delivery system of Atenolol.

Contact lens have been proposed as a mean of ocular drug delivery, but the conventional soaking method to load hydrophobic drugs, such as latanoprost shows low drug loading and high burst release with alteration in the critical lens properties. In this paper, a novel latanoprost-loaded PEGylated solid lipid nanoparticles (LP-pSLNs) were developed to increase the latanoprost loading capacity of contact lenses (LP-pSLN-L), while also sustaining ocular drug delivery. The pSLNs were spherical in shape with an average size of 105‒132 nm (nanometer) and a zeta potential ranging from ‒29.1 to ‒26.7 mV (millivolt). The LP-pSLNs led to improved swelling, transmittance, and protein adherence of the lens compared to the non-pegylated SLNs congeners (LP-SLN-L) and conventional soaked lens (LP-SM-L). The LP-SM-L lens showed low drug loading, high burst release, and a short release duration of 24 h. The LP-SLN-L and LP-pSLN-L lenses showed high drug uptake and sustained drug release up to 120 h and 96 h, respectively. The pegylation reduced the size of nanoparticles and improved the drug loading capacity, while the release rate was high in the initial hours. The LP-pSLN-L lens was found to be safe based in histopathological studies. In animal studies, the LP-pSLN-10-L batch showed high drug concentration at all-time points up to 96 h compared to the LP-SM-L and eye drop solution. In conclusion, pSLNs improved the latanoprost loading in the contact lens and showed sustained drug release, and thus can be used as a substitute to eye drop therapy.

Background Pseudomonas aeruginosa, a major respiratory pathogen, has been isolated from peri-implant sites and is associated with dental implant failure. This in-vitro study (part 1) aimed to fabricate a novel mucoadhesive silver nanoparticle-based local drug delivery chip, evaluate its antimicrobial efficacy against P. aeruginosa, and its safety for the treatment of peri-implantitis. Materials and methods Silver nanoparticles were synthesized and characterized using a transmission electron microscope (TEM). The local drug delivery chip was fabricated using gelatin, glycerol, silver nanoparticle solution (2.5 μg/ml, 5 μg/ml, 7.5 μg/ml, and 10 μg/ml), glutaraldehyde, and sodium alginate solution. These chips were evaluated for physical parameters, effect on viability of murine macrophage cell line J774A.1, and antimicrobial activity (using Kirby-Bauer disc diffusion method with 18 h incubation period) against P. aeruginosa ATCC 27853. Results Silver nanoparticle antimicrobial chip exhibited dimensions of 4 mm × 5 mm x 0.4 mm, 5.8 mg weight, pH 5–6, folding endurance 1.04, and one-year stability. P. aeruginosa was susceptible to ≥ 7.5 μg/ml concentration of silver nanoparticles (spherical shape with particle size ranging from 10 to 100 nm). Murine macrophage cells exhibited 93% viability after 24 h incubation with silver nanoparticle chips. Conclusion The novel silver nanoparticle chip showed dimensional stability, minimal effect on murine macrophage cell viability, and significant antimicrobial activity against P. aeruginosa. With the further establishment of its effective dosage and safety, this chip could be used as an adjunct to mechanical debridement (as a non-aerosol generating procedure) in treating peri-implantitis, especially during the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Humans are continuously plagued by number of new uncured diseases, resulting in the search of new medicines with zero level side effects. In the present study, an attempt has been made to prepare, characterize and to test the wound healing activity of chitosan based hydrogel. Shrimp shells was collected from Cuddalore (Lat 11° 42 N Long 79° 46 E), Annankovil (Lat. 11°30.47 N; Long. 079°47. 02E) and Mudasalodai landing centre (11o29 ′N 79o46 ′E) (Southeast coast of India) for extraction of chitin and chitosan and further characterized by FTIR, 1H – NMR, DSC, SEM and XRD. Poly Ethylene Glycol (PEG) is used as a cross linking agent for the preparation of chitosan hydrogel. The prepared hydrogel was characterized by FTIR, SEM, DSC and its swelling property was tested. Synthesized chitosan hydrogel was shown very good level of growth inhibition activity against human pathogens and wound healing activity within 12 h to 24 h. Thus the present study suggests the possibility of utilizing seafood waste of crustacean shells for the extraction and preparation of useful biologically active compounds like hydrogel for medicinal drug delivery and therapeutic applications.

Hyaluronic acid (HA), a natural polymer, has gained much attention recently because of its good biocompatibility and extensive availability. Herein, a novel drug delivery system based on hyaluronic acid-tetraphenyl ethylene conjugate (HA-SS-TPE) with glutathione (GSH)-responsiveness for targeted drug delivery is designed. During the self-assembly of HA-SS-TPE, doxorubicin (DOX) is loaded to form DOX-loaded polymeric micelles. These as-prepared DOX-loaded polymeric micelles not only exhibit fluorescent emission, but also fast glutathione-triggered dissociation to unload DOX by responding to tumor microenvironments. In-vitro investigations showed that the DOX-loaded polymeric micelles presented a higher intracellular release ratio in CD44-positive cells (ES2 and Hela) than in CD44-negative cells (MCF-7 and L929). Notably, in vivo investigations showed that DOX@HA-SS-TPE significantly suppressed tumor growth. As a result, such a GSH-responsive drug delivery system with fluorescent feature provides a potential treatment for CD44-overexpressing cancers.

Ultrasound-mediated approach has attracted more attention for the enhanced localized drug delivery in tumor chemotherapy. Here, well-defined PEGylated dendritic polyurethane (Ph-DPU-PEG) was synthesized via a facile one-pot method. It could easily form unimolecular micelles for chemotherapeutic drug delivery. Because the drug was encapsulated in the hydrophobic cores, the drug-loaded unimolecular micelles (DOX@Ph-DPU-PEG) could be hardly released without ultrasound, regardless the acidity of the releasing media. However, they showed an excellent ultrasound-triggered intracellular drug release performance, with a cumulative drug release of 81.6% in the simulated tumor intracellular microenvironment within 12 h. Furthermore, the ultrasound-triggered intracellular drug release was revealed with the CLSM technique, and an enhanced tumor growth inhibition was achieved on the HepG2 cells than free DOX.

Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI., Graphical abstract Image 1, Highlights • Alginate (ALG) alone has a limited vascularized ability in vivo. • ALG with 20% hyaluronic acid (HA) could attenuate LV remodeling and promote angiogenesis. • ALG-HA with lyophilized platelet-rich fibrin (Ly-PRF) could make further improvement in angiogenesis. • The Ly-PRF is promising for further clinical application because of autologous source and definite therapeutic effects.

Recent advances in drug delivery have made it possible to release bioactive agents from neural implants specifically to local tissues. Conducting polymer coatings have been explored as a delivery platform in bioelectronics, however, their utility is restricted by their limited loading capacity and stability. This study presents the fabrication of a stable conducting polymer hydrogel (CPH), comprising the hydrogel gelatin methacrylate (GelMA), and conducting polymer polypyrrole (PPy) for the electrically controlled delivery of glutamate (Glu). The hybrid GelMA/PPy/Glu can be photolithographically patterned and covalently bonded to an electrode. Fourier-transform infrared (FTIR) analysis confirmed the interpenetrating nature of PPy through the GelMA hydrogels. Electrochemical polymerisation of PPy/Glu through the GelMA hydrogels resulted in a significant increase in the charge storage capacity as determined by cyclic voltammetry (CV). Long-term electrochemical and mechanical stability was demonstrated over 1000 CV cycles and extracts of the materials were cytocompatible with SH-SY5Y neuroblastoma cell lines. Release of Glu from the CPH was responsive to electrical stimulation with almost five times the amount of Glu released upon constant reduction (-0.6 V) compared to when no stimulus was applied. Notably, GelMA/PPy/Glu was able to deliver almost 14 times higher amounts of Glu compared to conventional PPy/Glu films. The described CPH coatings are well suited in implantable drug delivery applications and compared to conducting polymer films can deliver higher quantities of drug in response to mild electrical stimulus. Statement of significance Conducting polymer hydrogels (CPH) have been explored for the electrically controlled release of bioactives from implantable devices. Typically, the conducting polymer component does not fully penetrate the hydrogel. We report, for the first time, a completely interpenetrating CPH allowing for the full benefits of the composite material to be realised, the hydrogels provide a reservoir for drug delivery, and conducting polymer renders the material responsive to electrical stimulation for drug release. We report a CPH for the electrically controlled delivery of glutamate (excitatory neurotransmitter) where several-fold more glutamate can be delivered compared to conducting polymer films. The described CPH coatings are well suited for use in bioelectronic devices to deliver large quantities of drug in response to mild electrical stimulus.

Designing stimuli-responsive therapeutic scaffolds to deliver hydrophobic chemo drugs with controlled and sustained release at the tumour site would be promising in cancer treatment. In a quest for the stimuli-responsive drug delivery system with sustained release, herein we have fabricated active pharmaceutical ingredient based ionic liquid (IL) based hydrogel with self-healable and injectable properties. The ionic hydrogel makes a localized, long-term co-delivery system with self-healable, injectable, and stimuli-responsiveness. Further, the smart hybrid ionic hydrogel was constructed through encapsulating doxorubicin (DOX) within the 3D matrix of the ionic hydrogel, which responds to an intracellular biological stimulus (e.g., pH and temperature) and releases the DOX in 57 h. Experimental results of IL-IL, IL-DOX interactions are supported through Density Functional Theory (DFT) calculations. In vitro cellular studies revealed that DOX loaded hybrid ionic hydrogel shows a synergistic anticancer effect against MCF-07 cells. These results demonstrate the ability of the ionic hydrogel as a promising candidate for local cancer therapeutics.

Metal-organic frameworks (MOFs) have recently allured a variety of concern in the fields of nanotechnology. However, exploring their biomedical applications is still a relatively new field. In this work, zeolite imidazole skeleton-8 (ZIF-8) was reported for the first time as a drug carrier for the treatment of lung injury. Uniform ZIF-8 nanoparticles encapsulating plumbagin (PLB) are achieved by a facile physical adsorption process. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and UV–vis absorption spectrum were conducted to investigate the physical properties of ZIF-8 and PLB@ZIF-8. In animal model, the collagen fibers deposition produced by severe lung injury is significantly decreased. The secretion of inflammatory factor TGF-β and IL-6 were efficiently dropped by the combination of plumbagin and ZIF-8. At the same time, the expressions of collagen I, α-SMA and TNF-α were also suppressed. This strategy puts forth a promising blueprint in the application of MOF materials, especially in biomedical fields.

Eudragit® RL (ERL) is pH independent copolymer. ERL is high permeability polymer with sustained released function; therefore, ERL is interesting polymer for the periodontal pocket drug delivery. The doxycycline hyclate (DH)-incorporated ERL-based in-situ forming matrix (ISF) was fabricated for intra-periodontal route employing 2-pyrrolidone (PYR) as a solvent. The various ERS concentrations in range of 10 to 25% w/w comprising 5% w/w DH in PYR were prepared as solution dosage forms. The viscosity of prepared formulations was polymeric concentration dependent (121 to 2134 cPs) with Newtonian-flow behavior. For 10, 15 and 20% w/w ERL solutions, there was no complete matrix formation after contact phosphate buffer solution pH 6.8 whereas the opaque solid matrix was apparently formed for 25% w/w ERL solution. Therefore, in situ phase separation of 25% w/w ERL solutions was achieved. The time to reach more than 80% drug release were 10, 24, 24 and 48 h for ISFs comprising 10, 15, 20 and 25% w/w ERL, respectively. Thus, ISFs containing ERL dissolved in PYR showed a potential system to deliver DH by intra-periodontal route of administration. By comparison, the 25% w/w ERL solution were most suitable for antisolvent-based ISF development.

Liquid crystalline nanoparticles (Cubosomes) are unique structures for the effective delivery of many pharmaceutical drugs. The present study is aimed to develop and characterize novel cubosomal formulation containing dexamethasone (DMS). The cubosomes were incorporated into hydrogel for prolonged delivery of DMS to treat vitiligo. The cubosomes were prepared via top-down technique using different concentrations of glyceryl monooleate (GMO) (lipid phase), poloxamer 407 (P 407) (non-ionic surfactant), oleic acid (fatty acid) and water (aqueous phase). The formulated cubosomal formulations were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta size analyzer for their surface morphology, particle size and zeta potential. Further, they were evaluated for % entrapment efficiency and in-vitro drug release. The optimized F-12 formulation exhibited a particle size of 250.40 nm and a zeta potential of −36.10 ± 2.56 mV. The in-vitro drug release of 88.12% was achieved at 12th h. The F-12 formulation was incorporated into 1% carbopol 940 to form cubogel (CG). The F-12 loaded CG was evaluated for physical characteristics, pH, drug content, viscosity, spreadability, and in-vitro drug release studies. All the evaluation parameters for the CG formulation were said to be within the standard limits. The in-vitro drug release for DMS loaded CG was found to be 83.58% at end of 12 h, thus indicating its potential as a better sustained drug delivery system for vitiligo.

Porous ceramic microspheres are a desirable substance for bone tissue reconstruction and delivery applications. This study focuses on Mg–Ca silicate microspheres encapsulated in biodegradable poly (lactic-co-glycolic acid) (PLGA) to serve as a biocompatible carrier for the controlled release of vancomycin hydrochloride. In this regard, diopside (MgCaSi2O6), bredigite (MgCa7Si4O16), and akermanite (MgCa2Si2O7) powders were synthesized by sol-gel and subsequent calcination methods. Then, porous akermanite, diopside and bredigite microspheres of 700–1000 μm in diameter were fabricated by using carbon porogen, droplet extrusion and sintering, then loaded with the drug and eventually coated with PLGA. The bare microspheres showed a considerable burst release mode of the drug into a physiological medium, whereas PLGA coating of the microspheres reduced the burst release level. To investigate effective mechanisms governing in the drug release from the carriers, the contribution of burst, degradation, and diffusion was analyzed by the sequential quadratic programming algorithm method. It was found that the relative contribution of diffusion to bioresorption is ranked as diopside > akermanite > bredigite, whereas PLGA coating dominates the diffusion mechanism. The dental pulp stem cells cytocompatibility MTT assay of the microspheres also showed that the drug loading deteriorates but PLGA coating improves the cell biocompatibility significantly. Comparatively, the biocompatibility of the PLGA-coated microspheres was ranked as akermanite > diopside > bredigite, as a result of a compromise between the release of the constituting ions of the ceramic carriers and vancomycin molecules. It was eventually concluded that PLGA-coated Mg–Ca silicate microspheres are promising candidates for drug-delivery bone tissue engineering and dental bone grafting applications.

Oral route of administration is considered as most widely accepted route which is a potential site for drug delivery, direct access to systemic circulation and site of action. Bisphosphonates are the class of drugs which have been approved for clinical use in osteoporosis and other bone diseases. Bisphosphonates are very poorly absorbed from the GI tract and have limited bioavailability of less than 1% with adverse gastrointestinal effects in humans. The present work aimed to develop sublingual spray formulation using Risedronate sodium with combination of Pullulan gum and HPMC E5. Formulation of sublingual spray was developed by employing optimization technique. The optimized formulation was selected and evaluated for various pharmaco-technical parameters such as viscosity, spray angle, drug content per actuation, In-vitro drug diffusion study, Ex-vivo permeation study and In-vivo pharmacodynamics study by glucocorticoid induced model in rats. Pharmaco-technical parameter results of optimized formulation showed satisfactory results. Comparative In-vitro drug permeation and ex-vivo permeation studies showed maximum drug release of 85% for optimized formulation incorporated with permeation enhance transcutol. In-vivo pharmacodynamic study showed better efficacy in treatment animals with optimized formulation and thus newly developed risedronate sodium sublingual spray proved to be effective used in treatment of osteoporosis.

In the current study, an efficient method was developed for the preparation of phenothiazinium Schiff base ligand followed by the attachment to nanosilver mediated by egg white (lysozyme) as a catalyst and reductant under solvent-free conditions. The synthesized Schiff base ligand, nanosilver, and its complex were characterized by UV, IR, XRD, and NMR. Biological studies for Schiff base ligand, nanosilver, and its complex were investigated. The advantages of this method are environmentally benign process; the product can be isolated simply by filtration, simplicity, elimination of solvents, high product yields, and short reaction times. The synthesized compounds were tested for their in vitro antimicrobial activity using the broth dilution method against Staphylococcus aureus (gram-positive) and E. coli (gram-negative) bacteria. From the results the silver nanocomplex exhibits enhanced antibacterial activity which may be due to the interaction of Schiff base and nano Ag on the bacterial cell wall. The silver complex can be utilized in the future for drug delivery and biomedical applications.

Nanofibrous materials are used in drug delivery as carriers of active ingredients. These can be incorporated into the materials with various electrospinning methods that differ mainly in the way spinning solutions are prepared. Each method affects primarily the encapsulation efficiency and distribution of active ingredients in the materials. This study focuses on the incorporation of octenidine dihydrochloride (OCT) and triclosan (TRI) into nanofibrous materials electrospun from native hyaluronic acid emulsions, dispersions, and blends. OCT had no substantial effect on fiber morphology, which is affected by the solvent system. All OCT encapsulation efficiencies were comparable (approximately 90%). TRI encapsulation efficiencies varied greatly depending on the method used. Merely 3% of TRI was encapsulated when it was spun from a dispersion. Encapsulation efficiency was higher, and TRI was incorporated in clusters when an emulsion was used. The best result was achieved with a blend, in which case 96% of TRI was encapsulated.

Despite tremendous advances in gas therapy, there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug delivery. Second near-infrared (NIR-II) window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive nature. In this study, we engineered an NIR-II laser-activated theranostic agent (named CP-bF@PEG) that was composed of amphiphilic polymers (Pluronic F127, with polyethylene glycol, PEG, moieties) coated with an NIR-II-absorbing conjugated polymer (PTTBBT, CP) and nitric oxide (NO) donor (benzofuroxan, bF), which served as an NIR-II photothermal inducer and NO nanogenerator. Under deep tissue penetration of NIR-II laser irradiation, CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal effect. Moreover, CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable manner. This NIR-II-absorbing polymer for high-contrast NIR-II fluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy, as evidenced by pronounced tumor therapeutic efficacy and few side effects. This nanotheranostic agent is a highly promising candidate for high-contrast NIR-II imaging-guided precision photothermal therapy combined with gas therapy against cancer.

Background: In the current era, the development of molecular techniques involves nano techniques, and the synthesis of nanoparticles is considered the preferred field in nanotechnology. Objective: The aim of the present work is to analyze the anticancer activity of the thymoquinone conjugated ZnO nanoparticles and understand its mechanism of action in triple-negative breast cancer cell lines MDA-MB-231. Methods: Zinc Oxide (ZnO) nanoparticles have extensive applications, and it was synthesized using a chemical precipitation method. Thymoquinone (TQ) is the major bioactive component of the seeds of Nigella sativa. Synthesized nanoparticles were characterized using various spectroscopic techniques. Thymoquinone-coated nanoparticles were checked for their efficiency. The cytotoxicity of ZnO, TQ, and TQ conjugated ZnO nanoparticles against MDA-MB-231. Colony-forming and cell migration assays were performed to measure the proliferative competence of the breast cancer cells on exposure to nanoparticles. The mechanism of apoptosis was probed by assessing MMP, interplay between ER stress and ROS. Results: The results of the characterization techniques confirmed that the particles synthesized were ZnO and TQ-ZnO nanoparticles. pH dependent release of the compound was observed. The anti-proliferative effect that impairs the formation of the colony was found to be enhanced in cells exposed to combined treatment with the nanoconjugate. Conclusion: Hence, the TQ conjugated ZnO nanoparticles can act as an efficient carrier for drug delivery at the target site in TNBC cells.

The nano-drug delivery system utilizing the ligand functionalized nanoparticles have a tremendous application in cancer therapeutics. The present study was aimed to fabricate the p-Coumaric acid-loaded aptamer (ligand) conjugated starch nanoparticles (Apt-p-CA-AStNPs) for effective treatment of triple-negative breast cancer (MDA-MB-231). The FT-IR spectrum stipulated the presence of functional groups associated with para-Coumaric acid (p-CA) and amino starch (AS) in p-CA-AStNPs. Further, the conjugation of aptamer in p-CA-AStNPs was confirmed by agarose gel electrophoresis. Transmission electron microscopic analysis revealed that the synthesized Apt-p-CA-AStNPs were less agglomerated. The zeta size analyzer displayed the average particle size as 218.97 ± 3.07 nm with ȥ-potential −29.2 ± 1.35 mV, and PDI 0.299 ± 0.05 for Apt-p-CA-AStNPs. The drug encapsulation and loading efficiencies were 80.30 ± 0.53% and 10.35 ± 0.85% respectively for Apt-p-CA-AStNPs. Apt-p-CA-ASNPs showed a rapid and bursting release in the initial five hours of the experiment in pH 5.4. A significant change was found in their cytotoxic efficacy between the samples: p-CA, p-CA-AStNPs, and Apt-p-CA-AStNPs. Among the tested samples, Apt-p-CA-AStNPs caused higher cytotoxicity in MDA-MB-231 cells through ROS regulation, nuclear damage, mitochondrial membrane potential, and apoptosis-related protein expressions. Overall, these results proved that Apt-p-CA-AStNPs were efficiently inhibited the MDA-MB-231 cells by regulating apoptosis.

Periodontitis is a chronic inflammatory disease of gum resulting from Porphyromonas gingivalis infectious at periodontal pockets. In situ forming gel (ISG) effectively delivers the antimicrobial agents to this targeted site. This study was to develop the dimethyl sulfoxide (DMSO) removal-based ISGs of Eudragit®L and their physicochemical properties were evaluated including the viscosity, rheological behavior, in vitro matrix formation, in vitro doxycycline hyclate (DH) release and antimicrobial activities. The ISGs showed the Newtonian flow which an increase in Eudragit®L amount enhanced a viscosity. They transformed into an opaque gel after exposure a simulated crevicular fluid and modulated the DH release longer than 3 days. The percentage of drug release from DMSO removal-based ISG containing 10, 15, 20 and 25% w/w of Eudragit®L was 95.9, 90.5, 79.8 and 70.0, respectively. Thus, DH release depended on the amount of Eudragit®L loading and corresponded with the polymeric matrix formation. The high Eudragit®L loading formulation retarded notably on the solvent removal owing to a thicker gel barrier. The DH-loaded in situ solvent removal-based Eudragit®L/ DMSO forming gels presented the efficient antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans and Porphyromonas gingivalis. Therefore, Eudragit®L/DMSO ISG exhibited as a potential periodontal pocket drug delivery system based on solvent removal mechanism.

Orthopaedic implant related infections are one of the major problems in orthopedic surgery and a major causes of implant failure. Local drug delivery is the significant approach to solve this problem. Bioactive implant materials coupled with antibiotics are widely used for the treatment of osteomyelitis. Gentamicin sulfate (GS) is mostly developed as an antibiotic to prevent bone implant related infection, due to cheap, broad antibacterial spectrum of action, and good stability. In the present study, a series of Gentamicin sulfate loaded chitosan combine with aloe vera (CS/AV) on Ti alloy has been synthesized by using electrodeposition method. Drug loaded CS/AV composite revealed higher antibacterial activity against S. aureus and E. coli. The loading of Gentamicin sulfate onto CS/AV nanoparticles does not considerably affect the bioactivity and cytocompatability. Consequently synthesized Gentamicin sulfate loaded CS/AV composite can be potential candidates for the treatment of osteomyelitis.

Covalent crosslinked stimuli-destructible hydrogels with the ability of irreversible stimuli-controlled bond dissociation have attracted great attentions due to their easy preparation, biocompatibility, biodegradability, stability against hydrolysis, and controlled solubility by applying desired triggers. Stimuli-controlled microstructure, elasticity, and mechanical properties has resulted in their application in selective capturing, proliferation, and detection of human and bacterial cells, drug delivery, wound dressing, and imprint lithography. Polymerization approaches and different functional groups required to prepare these hydrogels with the ability of irreversible bond dissociations, mechanism of stimuli-controlled bond cleavage, degradation products, comparison between the stimulants, and their final applications are highlighted in this review. Photocleavable hydrogels containing nitrobenzyl, coumarin, and perylene drivatives, redox-dissociable hydrogels containing diselenide and succinimide thioether bonds, destructible hydrogels prepared from phenolic ester and aldazine moieties as pH-cleavable bonds, and hydrogels crosslinked by enzyme- and thermo-dissociable moieties are the most important chemically crosslinked stimuli-destructible hydrogels, which show stimuli-controlled covalent bond dissociation with an irreversible mechanism.

Posterior capsular opacification (PCO) is the main postoperative complication after intraocular lens (IOL) implantation in cataract surgery, because of the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Drug-eluting IOLs, aimed to develop an in situ drug delivery device, are the promising concept in recent years. As IOLs are optical devices other than implants, the feasibility and applicability remain a challenge for drug-eluting coatings. In this investigation, a centrifugally concentric ring-patterned drug-loaded poly(lactide-co-glycolic acid) (PLGA) coating was designed and fabricated by the spin coating technique. The concentric ring-patterned morphologies and the drug loading and release properties were carefully investigated, and the spin coating parameters were optimized. A concentric annular coating with a thin center and thick periphery was obtained, which was particularly suitable for the surface modification of IOLs, as the visual pathway of the intraocular light transmission greatly requires good light transmittance of the IOLs. IOLs with the immunosuppressant cyclosporin A (CsA)-loaded coating (CsA @ PLGA) modification were then fabricated for PCO prevention. The in vitro LECs culture results showed that the CsA @ PLGA coating-modified IOLs significantly inhibited cell proliferation and induced cell death. Western blot analysis showed that the efficient cell inhibition behavior of CsA was due to the autophagy-mediated cell death pathway. The in vivo intraocular implantation results confirmed the desired PCO inhibition effect. Thus, the centrifugally concentric ring-patterned drug-loaded PLGA coating obtained by the spin coating technique provides a simple yet effective alternative of IOL modification for PCO prevention. Statement of Significance • Concentric ring-patterned polymer coating, specifically for drug-eluting IOL fabrication, was developed by the spin coating technique. • The immunosuppressant CsA inhibited LEC proliferation through the autophagy-mediated cell death pathway. • Concentric ring-patterned CsA-eluting IOLs exhibited reliable in vivo PCO prevention. • The drug-eluting IOLs fabricated by the simple and economical spin coating technique have a great potential in clinical translation.

The present study was intended for development of hydrogel-based drug delivery system with wound healing potential. The honey-based hydrogels were prepared by cold mechanical method. Carbopol-940 and Chitosan (75% deacetylated) were used as polymers. Triethanolamine was used as a pH adjuster. Methyl paraben was used as preservative and propylene glycol as an emollient. The developed hydrogels were characterized for pH, viscosity, swelling index, spreadability, drug content, in-vitro permeation studies using dialysis membrane and in-vivo wound healing activity by excision wound model. The results indicated the acceptability of the prepared hydrogels by the evaluation tests. The in-vitro permeation studies showed that release of honey varied according to the percentage of honey and the polymer used in the hydrogels. Formulation F14 was found to be the best formulation with cumulative percent drug release of 90.75% and showed greater rate of wound healing within 12 days. Hence, the results of this research work showed that the developed hydrogels can provide a better delivery system for wound healing.

Transformation of paclitaxel, an FDA (Food and Drug Administration) approved highly potent anticancer drug, to its nano dimensions was achieved using bioenhancers namely piperine and quercetin. After addition of bio enhancer, paclitaxel nanoparticles expressed better solubility and bioavailability in comparison to free paclitaxel. The size, morphology, entrapment efficiency, diffusion pattern, cytotoxicity and pharmacokinetic behaviour were studied for the transformed drug. The shape and size of paclitaxel mixed with piperine and quercetin were characterized by transmission electron microscopy (TEM). The particle size was found between 95 nm and 155 nm having oval shape. The entrapment efficiency of particles was found to be increased with the addition of bioenhancers and the cytotoxicity of the particles was also found in acceptable range. The observations suggest the nano transformation of paclitaxel and addition of bioenhancers may enhance the efficacy of anticancer activity of paclitaxel.