Polyelectrolyte Complexation Method Research Articles

Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.

Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.

Leucaena leucocephala succinate based polyelectrolyte complexes for colon delivery of synbiotic in management of inflammatory bowel disease

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.

Ascorbic acid nanoencapsulation using polyelectrolyte complex formation and optimization using hybrid artificial neural network‐genetic algorithm

AbstractBackgroundsThe polyelectrolyte complex (PEC) formation using chitosan (Cs) and alginate (Alg) has been employed to carry out Vitamin C (VC) nanoencapsulation because of its instability in adverse conditions. This method includes VC nanoencapsulation using physical cross‐linking. The effect of the mixing order as well as the different mass ratios of both the polymer and the VC content, were investigated on the size, pdi, zeta potential, encapsulation efficiency (EE%), and yield%. Hence, considering different mass ratios of both polymer (4:1–1:4) and VC content (10%–30% w/w of Cs) as independent variables, PECs were formed using 0.1% (w/v) of Cs and Alg solution.ResultThe result showed that, for equal mass ratio (1:1) of Cs and Alg, the addition of Alg solution to Cs solution led to lower particle size, while higher particle size was observed with reverse order of addition. However, no significant effect of polymer mass ratios was observed on particle size and NPs stability, while EE varied with VC concentration. Artificial neural network (ANN) was applied to train the experimental parameters Cs: Alg ratios (X1:X2) and VC content (X3) for the output variables. Moreover, process optimization was carried out using multi‐objective genetic algorithm (MOGA) with the goal of lowering particle size and increasing EE while increasing nanoparticle yield.ConclusionThe PEC method effectively encapsulated VC as obtained from higher EE. The Cs: Alg ratio of 4:2.1 and 18% VC content (w/w of Cs) was found optimum for nanoencapsulation. The final ANN‐GA model showed an acceptable agreement with experimental data.

Fabrication, characterization and evaluation of a new designed botulinum toxin-cell penetrating peptide nanoparticulate complex.

To have a better and longer effect, botulinum neurotoxin (BoNT) is injected several times in a treatment course, which could increase side effects and cost. Some of the most cutting-edge strategies being investigated for proteins to their physiologic targets involve the reformulation of BoNT based on peptide-based delivery systems. For this purpose, cell-penetrating peptides (CPPs) are of particular interest because of their capacity to cross the biological membranes. A short and simple CPP sequence was used as a carrier to create nanocomplex particles from BoNT/A, with the purpose of increasing toxin entrapment by target cells, reducing diffusion, and increasing the duration of the effect. CPP-BoNT/A nanocomplexes were formed by polyelectrolyte complex (PEC) method, considering the anionic structure of botulinum toxin and the cationic CPP sequence. The cellular toxicity, and absorption profile of the complex nanoparticles were evaluated, and the digit abduction score (DAS) was used to assess the local muscle weakening efficacy of BoNT/A and CPP-BoNT/A. The provided optimized polyelectrolyte complex nanoparticles had a 244 ± 20nm particle size and 0.28 ± 0.04 PdI. In cellular toxicity, CPP-BoNT/A nanocomplexes as extended-release formulations of BoNT/A showed that nanocomplexes had a more toxic effect than BoNT/A. Furthermore, the comparison of weakening effectiveness on muscle was done among nanoparticles and free toxin on mice based on the digit abduction score (DAS) method, and nanocomplexes had a slower onset effect and a longer duration of action than toxin. Using PEC method allowed us to form nanocomplex from proteins, and peptides without a covalent bond and harsh conditions. The muscle-weakening effect of toxin in CPP-BoNT/A nanocomplexes showed acceptable efficacy and extended-release pattern.

Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment

Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.

Chitosan-Linseed mucilage polyelectrolyte complex nanoparticles of Methotrexate: In vitro cytotoxic efficacy and toxicological studies

The goal of this research was to develop, fabricate and analyze polymeric nanoparticles for the administration of methotrexate (MTX). Linseed mucilage and chitosan nanoparticles (NPs) were prepared using a slightly modified polyelectrolyte complex (PEC) method. The size, shape, and encapsulation effectiveness of the resultant nanoparticles were measured. MTX release profiles at gastrointestinal pH (1.2 and 7.4) and tumor pH (5.5) were examined to determine the targeted potential of NPs as pH-responsive nanocarriers. Zeta analysis showed that nanoparticles prepared by PEC have a size range of 192.1 nm to 246 nm, and PDI was 0.3 of the optimized formulation, which showed homogenous nature of prepared nanoparticles formulation. The findings demonstrated that NPs have a low polydispersity index and a positive zeta potential (PDI). The in-vitro release of the drug indicated a pH-dependent, sustained drug release up to 24 h. Blank LSMCSNPs had almost no in-vivo cytotoxicity for 14 days, while optimum MTX loaded NPs had strong antitumor effects on HepG2 and MCF-7 cells as measured by the MTT assay. Cell apoptosis induction was also checked and MCF-7 cells treated with MTX-LSMCSNPs had a significantly greater rate of apoptosis (21.2 %) than those treated with MTX alone (14.14 %). The findings show that LSMCSNPs could be a potential delivery mechanism for methotrexate to cancer cells in a secure, steady, and ideally controlled manner to improve therapeutic outcomes.

Preparation and Characterization of Chitosan/κ-Carrageenan Based Polymeric Nanoparticles for Gemcitabine Delivery

Cancer is the most fatal disease of the last century after cardiovascular disease. Gemcitabine is a nucleosideanalogue used in the treatment of cancer. However, like many anticancer drugs, it has many side effects thatlimit treatment. A nano drug delivery system has been developed to provide effective treatment by reducingside effects. Chitosan and κ-carrageenan, which are regarded as safe by the FDA, were used in the preparationof the nano drug delivery system. In the synthesis, pre-ionic gelation followed by polyelectrolyte complexationmethod was used and then a second ionic gelation step was added. Chitosan: κ-carrageenan ratio and CaCl2concentration were optimized and the optimum polymer ratio was determined as 6:1 and CaCl2 concentrationwas 2.5%. Its hydrodynamic size at optimum conditions was 393 nm and its size measured size in TEM was 20nm. FTIR analyzes showed that nanoparticle synthesis was successful. Drug loading was performed byencapsulation and 58% drug loading was achieved. After drug loading, the hydrodynamic dimension wasincreased to 595 nm and its size measured size in TEM 45 nm. Drug release was monitored for 95 hours andwas determined to be higher at pH 6.0 compared to 7.4 and pH sensitive. In addition, the Higuchi model is themost suitable mathematical model for drug release kinetics. The obtained results showed that chitosan: κcarrageenan nanoparticles were suitable for gemcitabine delivery and were pH sensitive enough to respond tothe tumor microenvironment.

Toxicity Assessment and Control of Early Blight and Stem Rot of Solanum tuberosum L. by Mancozeb-Loaded Chitosan-Gum Acacia Nanocomposites.

Biopolymers such as chitosan and gum acacia are used for nanotechnological applications due to their biosafety and ecofriendly nature. The commercial fungicide mancozeb (M) was loaded into chitosan–gum acacia (CSGA) polymers to form nanocomposite (NC) CSGA-M (mancozeb-loaded) measuring 363.6 nm via the ionic gelation and polyelectrolyte complexation method. The physico-chemical study of nano CSGA-M was accomplished using dynamic light scattering (DLS), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Nano CSGA-M-1.0 (containing 1.0 mg/mL mancozeb) at 1.5 ppm demonstrated a maximum inhibition (83.8 ± 0.7%) against Alternaria solani, while Sclerotinia sclerotiorum exhibited a 100% inhibition at 1.0 and 1.5 ppm through the mycelium inhibition method. Commercial mancozeb showed an inhibition of 84.6 ± 0% and 100%, respectively, for both fungi. In pot house conditions, NCs were found to exhibit good antimicrobial activity. Disease control efficiency (DCE, in %) in pathogen-treated plants for CSGA-M-1.0 was 64.6 ± 5.0 and 60.2 ± 1.4% against early blight and stem rot diseases, respectively. NCs showed lower cytotoxicity than commercial mancozeb at the given concentration. In conclusion, both in vitro and in vivo antifungal efficacy for nano CSGA-M was found to be quite comparable but less toxic than mancozeb to Vero cell lines; thus, in the future, this formulation may be used for sustainable agriculture.

Formulation and optimization of terbinafine HCl loaded chitosan/xanthan gum nanoparticles containing gel: Ex-vivo permeation and in-vivo antifungal studies

Superficial fungal infections require a therapeutic concentration of terbinafine HCl (TB) in the targeted skin tissue, hard to achieve after oral administration due to high protein binding. Therefore, the present study aimed to develop a polymeric nanoparticle-loaded gel system for topical terbinafine delivery with maximum drug retention in skin layers. Terbinafine loaded CH/XG nanoparticles produced by polyelectrolyte complexation method followed by incorporation in carbopol gel. All prepared formulations fell in a size range of 194.28–406.67 nm showing a significantly increasing trend by increasing the concentration of the polymer. Entrapment efficiency was amplified (up to 98.44%) by increasing the polymer concentration due to the increase in solution viscosity. Morphological characteristics of formulation revealed particles of round edges. FTIR analysis confirmed the compatibility of ingredients by showing no interaction between the drug and other components. Ex-vivo permeation studies revealed the drug's biphasic release (initial burst release for 2 h and then slow release) with maximum permeation of 13.95%. Percentage retention of the drug was up to 80.5%, which was significantly higher than marketed formulation. In vivo studies revealed that developed formulation provided a rapid and complete removal of the fungal burden compared to control and marketed formulation.

Stealth PEGylated chitosan polyelectrolyte complex nanoparticles as drug delivery carrier

PEGylated stealth nanoparticles have emerged as promising drug delivery carrier for cancer therapy. In this study, natural polycationic chitosan was grafted with poly(ethylene glycol) (PEG) to improve the water-solubility and long-circulation. Then PEGylated chitosan nanoparticles were formed by electrostatic interaction between sulfonic acid group of anionic functional polymer and protic amino group of PEGylated chitosan, using polyelectrolyte complex method. Effects of various factors on particle size and distribution, and the stability, biocompatibility, long-circulation ability were investigated. The results showed that when the concentration of PEGylated chitosan and anionic polymer was 0.20 mg/mL, pH of PEGylated chitosan was 5.0, pH of polymer was 5.5 and molar ratio (S/N) was 0.83, particle size of the prepared nanoparticles was 261.2 ± 5.5 nm with pdI of 0.070. Nanoparticles were relatively stable for more than 4 days under pH < 7.0 and normal saline conditions. The results of cytotoxicity experiments showed that the toxicity of PEGylated chitosan nanoparticles was greatly reduced, which met the basic requirements of biomedical materials. The cellular uptake efficiency of PEGylated chitosan nanoparticles was about 4 times lower than that of conventional chitosan nanoparticles, which indicated long circulation time of PEGylated chitosan nanoparticles in the blood. It was expected that this kind of stealth nanoparticles would have a broad application prospect in the field of drug delivery system.

P-selectin targeting polysaccharide-based nanogels for miRNA delivery

Nanogels were prepared in aqueous media without the use of any organic solvent via a simple polyelectrolyte complexation method between aminated pullulan and fucoidan followed by covalent crosslinking with genipin. Homogeneously distributed genipin crosslinked nanogels (G-PECs) were obtained with a mean hydrodynamic diameter of ~155 nm and zeta potential of 0.86 ± 4.35 mV. Their capacity to bind to human activated platelets was evaluated in vitro, as well as their cytocompatibility within human endothelial cells after 1 day of incubation up to 1000 µg/mL of G-PECs (94.56 ± 7.82% of viable cells). Additional hemolysis tests support the biocompatible character of the developed nanosystems (hemolysis rate of 2.09 ± 0.06% for 1000 µg/mL of G-PECs). Under acid conditions, the surface charge of G-PECs was tuned to around ~10 mV allowing miRNA incorporation via electrostatic interactions. G-PECs were able to promote miRNA delivery inside cells, as demonstrated by fluorescence microscopy images of labelled miRNA. With further studies to demonstrate the biological activity of delivered miRNA, these nanogels could be an interesting platform for miRNA-based therapeutics in atherothrombotic-related diseases thanks to the possibility to target over-expressed P-selectin.

CD44-specific A6 nano-short peptide enhances the targeting and mechanism of doxorubicin on the surface of polymers for multiple myeloma

In this study, we sought to prepare epirubicin immunonanoparticles and observe their antibody activity, drug release in vitro, and antitumor effects in vitro. Epirubicin nanoparticles (e-adm-nps) were synthesized using the polyelectrolyte complex method, and monoclonal antibody nanoparticles were synthesized using a chemical cross-linking method. The antibody activity of epirubicin monoclonal antibody nanoparticles (emadm ab nps) was detected by ELISA, the drug release in vitro was measured by ultraviolet spectrophotometry, and the cytotoxic effect in vitro was detected using a thiazole blue assay. The average particle size of e-adm-ab-nps was 190 (±21) mm, and the antibody activity was well preserved. in vitro drug release analysis showed that e-admab-nps had sustained-release characteristics, and the cumulative release of e-adm-ab-nps reached 93.46% in 10 days. The cytotoxic effect of e-adm in vitro was time-dependent over 1 to 6 days, and dose-dependent over 1 to 10 days, although the difference between e-adm-ab-nps and e-adm at the same concentrations was not statistically significant (P &gt; 0.05). E-adm-abnps show a sustained-release effect and immune activity, can prolong the effective time of e-adm for mouse multiple myeloma cells, and have no effect on the biological activity of epirubicin.

Preparation of PEG-grafted chitosan/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme

Streptokinase, as a thrombolytic drug, is widely used in treatment of cardiovascular disorders and deep vein thrombosis. Streptokinase is immunogenic due to its prokaryotic source, having short biological half-life (i.e. 15 to 30 min) that is not enough for an efficient therapy. In this study, nanoparticles (NPs) of chitosan/streptokinase and polyethylene glycol (PEG)-grafted chitosan/streptokinase were prepared by polyelectrolyte complex method. Particle size of chitosan and PEG-grafted chitosan NPs were 154 ± 42 and 211 ± 47 nm, respectively. Results showed that using PEG in preparation of nanoparticles leads to ~24% decrease in encapsulation efficiency. Encapsulation of streptokinase in the NPs also resulted in a slight reduction in enzymatic activity. However, in vivo findings indicated that response of the immune system was delayed for 20 days and blood circulation time of the enzyme increased up to 120 min by using PEG. Biological half-life of the drug also increased up to twice in PEG-grafted chitosan. In conclusion, PEG-grafted chitosan NPs could be an alternative for delivery of streptokinase to reduce its clinical limitations.

Antitumor efficacy of Folic Acid conjugated Polymeric Nanoparticles of SN-38 after oral delivery

The objective of the present research was to develop folic acid conjugated polymeric nanoparticles (FCsPNP) and to investigate its therapeutic effectiveness in xenograft Colon tumor models after oral delivery. Chitosan coated PLGA nanoparticles (CsPNP) were prepared by polyelectrolyte complexation method and it was further conjugated with Folic acid. Optimized formulation was investigated for particle size, zeta potential, polydispersity index (PdI), % entrapment drug loading and in vitro release. The morphology was observed by SEM and TEM images. Tumor regression studies were conducted on Balb/c mice implanted with Colo-26 cells. FCsPNP were successfully prepared and optimized. In vitro parameters viz. Particle size, Zeta potential, PdI were found to be optimum. The in vitro % release is directly correlated with the nature of polymers and folate conjugation. In vivo tumor regression studies found the formulations to be less toxic than Irinotecan hydrochloride (IHCl). CsPNP and FCsPNP were successfully prepared and evaluated for antitumor efficacy after oral delivery. FCsPNP were more effective in the colon tumor treatment and found to be less toxic than IHCl thus making it a potential drug delivery candidate for future anticancer therapy.&#x0D; Keywords: Nanoparticles, Xenograft colon tumor, Chitosan, Irinotecan hydrochloride

Comparison of Formulation Methods to Produce Nano-Chitosan as Inhibitor Agent for Bacterial Growth

Chitosan is known as an antibacterial agent. The effective surface area ratio of chitosan can be increased by modification into nanoparticles. Nano-chitosan can be prepared with several simple methods, i.e. precipitation, ionic gelation, or the polyelectrolyte complex method. This study compared these three methods in terms of the targeted product characteristics, i.e. stability of the average nanoparticle size as well as the colloidal dispersion, and the antibacterial characteristics. All three methods resulted in nanoparticle formation, but in the precipitation method significant zeta potential reduction was observed due to the presence of negative ions from the alkali that neutralized the chitosan amine group. The ionic gelation method yielded higher zeta potential and higher inhibition of bacterial growth than those yielded by the polyelectrolyte complex method. Ionic gelation and the polyelectrolyte complex method resulted in much better colloidal dispersion stability than the precipitation method, where a significant particle size increase was observed after one week of storage. This result indicates that both ionic gelation and the polyelectrolyte complex method can be used for forming nano-chitosan for the purpose of food preservation. However, for fishery products it is advisable to use the polyelectrolyte complex method because the TPP usually used in ionic gelation is not allowed to be applied to fish.

Selection of Polyanions as Complexation Agent in the Formation of Nanochitosan by Polyelectrolyte Complex Method

The aqueous dispersion of nanochitosan was prepared by polyelectrolyte complex (PEC) method with various mixing ratios of chitosan and polyanions, i.e., chitosan-glucomannan, chitosan-hyaluronic acid, and chitosan-Arabic gum. The formation of nanochitosan was carried out by adding the polyanion solution dropwise into the acid solution of chitosan. The study aimed to determine the best polyanion among the variations tested in this study, concerning the targeted particle size and the stability of the dispersion over time. Particle size distribution was observed by Particle Size Analyzer (PSA). The result indicated that Arabic gum gave the smallest average particle size, i.e. 192.5 nm, at a chitosan/polyanion mass ratio of 3:1 and pH value of 4.

Delivery of novel vancomycin nanoplexes for combating methicillin resistant Staphylococcus aureus (MRSA) infections

The development of novel antibiotic systems is needed to address the methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of the study was to explore the novel nanoplex delivery method for vancomycin (VCM) against MRSA using dextran sulfate sodium salt (DXT) as a polyelectrolyte complexing agent. Nanoplexes were formulated by the self-assembling amphiphile polyelectrolyte complexation method and characterized. The size, polydispersity index (PDI), and zeta potential (ZP) of the optimized VCM nanoplexes were 84.6 ± 4.248 nm, 0.449 ± 0.024 and −33.0 ± 4.87 mV respectively, with 90.4 ± 0.77% complexation efficiency (CE %) and 62.3 ± 0.23% drug loading. The in vitro (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)tetrazolium (MTT) studies of the nanoplexes were found to be non-toxic against different mammalian cell lines tested and may confirm its biosafety. While the in vitro drug release studies demonstrated sustained slower release. The in silico study confirmed the spontaneous interaction of VCM with DXT in the presence of sodium chloride. A 6.24-fold enhancement was observed for VCM nanoplexes via in vitro antibacterial studies. Flow-cytometric analysis showed effective cell killing of 67% from VCM nanoplexes compared to 32.98% from the bare vancomycin at the minimum inhibitory concentration (MIC) of 1.25 μg/mL. The in vivo studies using BALB/c mouse skin infection model revealed that nanoplexes reduced MRSA burden by 2.3-folds compared to bare VCM. The novel nanoplexes have potential to be a promising delivery system to combat MRSA infections for improved treatment of bacterial infections.

Effect of insulin-coated trimethyl chitosan nanoparticles on IGF-1, IGF-2, and apoptosis in the hippocampus of diabetic male rats.

Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema. The purpose of this research was to evaluate the effect of oral insulin-coated trimethyl chitosan nanoparticles on control of glycemic status, IGF-1 and IGF-2 levels, and apoptosis in the hippocampus of rats with diabetes mellitus. Insulin-coated trimethyl chitosan nanoparticles were prepared by the polyelectrolyte complex method (PEC) method. Insulin loading content, loading efficiency, quantity and quality of particle size were evaluated. In vivo study was performed in different treatment groups of male Wistar rats with diabetes mellitus by insulin-coated trimethyl chitosan nanoparticles or subcutaneous injection of trade insulin. The duration of diabetes was eight weeks and the treatment was started after that time and continued for another two weeks. Body weight, fasting blood glucose (FBS), hippocampal apoptosis, and immunohistochemical (IHC) protein levels of IGF-1 and IGF-2 were assessed at the end of the experiments. The size and polydispersity indexes were 533 nanometers and 0.533, respectively. Insulin coated trimethyl chitosan nanoparticles showed high loading efficiency (97.67% ) and loading content (48.83% ). The spherical shape of nanoparticle was confirmed by transmission electron microscopic (TEM). The amine, amide, ether and aliphatic groups were evaluated using FT-IR spectrophotometer which represented the correctness of the insulin coated trimethyl chitosan nanoparticles. Although the apoptotic index was not changed either by insulin-coated nano-particles or commercial insulin, in vivo results showed the efficacy of insulin-coated nanoparticles as well as commercial insulin in compensated weight loss, FBS and protein levels of IGF-1 and IGF-2. The present study showed the efficacy of insulin coated nanoparticle in oral route manner that can be tested in Phase I- III clinical trials. However, a behavioral study could reveal the efficacy of insulin-loaded nanoparticles in the improvement of cognitive changes through the modulation of IGF-1 and IGF-2 levels in the hippocampus.

The Preparation and Medical Applications of Chitosan Microspheres

Background: The microsphere prepared from chitosan, a natural polymeric material, has attracted considerable attentions due to the natural instincts of chitosan and microsphere structure. Objective: In the current review, the recent progress on the preparation and medical applications of chitosan microspheres would be introduced and summarized. Method: The methods for the preparation of CS microspheres were summarized, such as emulsion crosslinking method, coacervation method, precipitation method and polyelectrolyte complexation method, and so on. The tunable chemical properties possessed by CS microsphere, such as easily modified structure, and excellent biological properties including lower cytotoxicity, biocompatibility and biodegradability, would be introduced. Its medical applications based on its amazing properties in the recent years were present in detail with emphasis on the progress and advancement in drug delivery, gene therapy, bone repair, tissue engineering and wound dressing. Conclusion: It was believed that the rapid development of novel preparation technology will bring broader application prospects to CS microspheres. Keywords: Chitosan, microspheres, preparation, medical application, lower cytotoxicity, biocompatibility and biodegradability.