A temperature-induced and shear-reversible assembly of latanoprost-loaded amphiphilic chitosan colloids: Characterization and in vivo glaucoma treatment

Hydrogels composed of assembled colloids is a material class that is currently receiving much interest and shows great promise for use in biomedical applications. This emerging material class presents unique properties derived from the combination of nanosized domains in the form of colloidal particles with a continuous gel network and an interspersed liquid phase. Here we developed an amphiphilic chitosan-based, thermogelling, shear-reversible colloidal gel system for improved glaucoma treatment and addressed how preparation procedures and loading with the anti-glaucoma drug latanoprost and commonly used preservative benzalkonium chloride influenced the mechanical properties of and drug release from the colloidal gels. The results highlight that incorporated substances and preparation procedures have effects both on mechanical properties and drug release, but that the release of drug loaded in the colloidal carriers is mainly limited by transport out of the carriers, rather than by diffusion within the gel. The developed colloidal chitosan based gels hold outstanding biomedical potential, as confirmed by the ease of preparation and administration, low cytotoxicity in MTT assay, excellent biocompatibility and lowering of intraocular pressure for 40 days in a rabbit glaucoma model. The findings clearly justify further investigations towards clinical use in the treatment of glaucoma. Furthermore, the use of this shear-reversible colloidal gel could easily be extended to localized treatment of a number of critical conditions, from chronic disorders to cancer, potentially resulting in a number of new therapeutics with improved clinical performance.     

Chitosan nanoparticle/PCL nanofiber composite for wound dressing and drug delivery

Many investigations of wound dressings equipped with drug delivery systems have recently been conducted. Chitosan is widely used not only as a material for wound dressing by the efficacy of its own, but also as a nanoparticle for drug delivery. In this study, an electrospun polycaprolactone nanofiber composite with chitosan nanoparticles (ChiNP–PCLNF) was fabricated and then evaluated for its drug release and biocompatibility to skin fibroblasts. ChiNP–PCLNF complexes showed no cytotoxicity and nanoparticles adsorbed by van der Waals force were released into aquatic environments and then penetrated into rat primary fibroblasts. Our studies demonstrate the potential for application of ChiNP–PCLNF as a wound dressing system with drug delivery for skin wound healing without side effects.     

Effect of different polymers and their combinations on the release of metoclopramide HCl from sustained-release hydrophilic matrix tablets

Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.     

Preparation,characterization and bioactivities of nano anhydrous calcium phosphate added gelatin–chitosan scaffolds for bone tissue engineering

Abstract

Gelatin, chitosan and nano calcium phosphate based composite scaffold with tailored architectures and properties has great potential for bone regeneration. Herein, we aimed to improve the physico chemical, mechanical and osteogenic properties of 3D porous scaffold by incorporation of dihydrogen calcium phosphate anhydrous (DCPA) nanoparticles into biopolymer matrix with variation in composition in the prepared scaffolds. Scaffolds were prepared from the slurry containing gelatin, chitosan and synthesized nano DCPA particle using lyophilization technique. DCPA nano particles were synthesized using calcium carbonate and phosphoric acid in water–ethanol medium. XRD pattern showed phase pure DCPA in synthesized nanopowder. Scaffolds were prepared by addition of DCPA nanoparticles to the extent of 5–10?wt% of total polymer into gelatin–chitosan solution with solid loading varying between 2.5 and 2.75?wt%. The prepared scaffold showed interconnected porosity with pore size varying between 110 and 200 micrometer. With addition of DCPA nanoparticles, average pore size of the prepared scaffolds decreased. With increase in nano ceramic phase content from 5?wt% to 10?wt% of total polymer, the compressive strength of the scaffold increased. Scaffold containing 10?wt% DCPA showed the highest average compressive strength of 2.2?MPa. Higher cellular activities were observed in DCPA containing scaffolds as compared to pure gelatin chitosan scaffold suggesting the fact that nano DCPA addition into the scaffold promoted better osteoblast adhesion and proliferation as evident from MTT assay and scanning electron microscopic (SEM) investigation of osteoblast cultured scaffolds. A higher degree of lamellopodia and filopodia extensions and better spreading behavior of osteoblasts were observed in FESEM micrographs of MG 63 cultured DCPA containing scaffold. The results demonstrated that both mechanical strength and osteogenic properties of gelatin–chitosan scaffold could be improved by addition of anhydrous dihydrogen calcium phosphate nanoparticles into it.     

A型肉毒杆菌毒素的壳聚糖／海藻酸钠缓释微囊研制和药物的体外释放速率研究

目的：研制包裹A型肉毒杆菌毒素的壳聚糖/海藻酸钠微囊,并测定其体外药物释放动力学。方法：采用注射器滴注法制成包裹A型肉毒杆菌毒素的壳聚糖/海藻酸钠微囊混悬液。采用高效液相色谱法测定A型肉毒杆菌毒素的标准曲线,每隔2周测定微囊所包裹的A型肉毒杆菌毒素体外释放浓度。结果：微囊形态为圆形透明颗粒状,粒径在1mm左右。用SPSS统计软件进行分析微囊中A型肉毒杆菌毒素的体外每2周释放量,显示药物累积释放量与时间之间为直线关系,基本符合药物零级释放动力学。结论：滴注法制备包裹A型肉毒杆菌毒素的壳聚糖/海藻酸钠缓释微囊制作方法简便,其药物体外释放稳定。     

VNA改性壳聚糖对阴离子染料普施安红的吸附性能

通过一步自由基聚合法,采用新壬酸乙烯酯(VNA)疏水改性壳聚糖(Cts),制得改性产物VNA-Cts。通过红外光谱和热重分析对产物进行了表征,并研究了其作为吸附剂对阴离子染料普施安红(MX-5B)的吸附能力。结果表明:VNA基团被成功地接枝到Cts主链上,VNA-Cts的最大吸附能力与Cts含量呈线性相关性,接枝率为27.2%的VNA-Cts(CtsD_27.2)具有良好的耐酸性、热稳定性和吸附染料的高效性,并且其最大饱和吸附量为1 180 mg/g;吸附模型符合Langmuir吸附等温模型和Pseudo-secongd-order动力学模型;将吸满染料的CtsD_27.2置于pH为8的NaOH溶液中,大约80%的染料会解吸附重新回到水溶液中。     

Chitosan/gelatin porous scaffolds containing hyaluronic acid and heparan sulfate for neural tissue engineering

The novel chitosan (Cs)/gelatin (Gel) porous scaffolds containing hyaluronic acid (HA) and heparan sulfate (HS) were fabricated via freeze-drying technique, and their physicochemical characteristics including pore size, porosity, water absorption, and in vitro degradation and biocompatibility were investigated. It was demonstrated that the Cs/Gel/HA/HS composite scaffolds had highly homogeneous and interconnected pores with porosity above 96% and average pore size ranging from 90 to 140?μm and a controllable degradation rate. The scanning electron microscopic images, cell viability assay, and fluorescence microscopy observation revealed that the presence of HA and HS in the scaffolds significantly promoted initial neural stem and progenitor cells (NS/PCs) adhesion and supported long-time growth in three-dimensional environment. Moreover, NS/PCs also maintained mutilineage differentiation potentials with enhanced neuronal differentiation upon induction in the Cs/Gel/HA/HS composite scaffolds in relation to Cs/Gel scaffolds. These results indicated that the Cs/Gel/HA/HS composite scaffolds were suitable for neural cells’ adhesion, survival, and growth and could offer new and important options for neural tissue engineering applications.     

Alginate/quaternized carboxymethyl chitosan/clay nanocomposite microspheres: preparation and drug-controlled release behavior

Drug-delivery systems, using natural drug carriers, have become increasingly important because of their nontoxicity and biodegradability. In this study, firstly, quaternized carboxymethyl chitosan (QCMC) was intercalated into the interlayer of organic montmorillonite (OMMT) to obtain the QCMC/OMMT nanocomposites, their structure, morphology, and thermal stability were investigated. Next, crosslinked alginate/QCMC/OMMT (AQCOM) microsphere was obtained by crosslinking with CaCl₂, and the drug-controlled release behavior was evaluated with bovine serum albumin (BSA) as model drug. The results suggested that, carboxyl groups in alginate and QCMC crosslinked with Ca²⁺, quaternary ammonium groups in QCMC or OMMT electrostatically interacted with carboxyl groups in alginate, and there was stable three-dimensional network in AQCOM microsphere. The swelling ratio of AQCOM microspheres decreased with the increase of OMMT content, the lowest one was only about 45% compared to the microsphere without OMMT of 197%. Besides, the in vitro release results for BSA indicated that the AQCOM microsphere displayed more excellent encapsulation and controlled release capacities than the microsphere without OMMT. The in vitro active cutaneous anaphylaxis test was carried out on Guinea pigs, which revealed that AQCOM microsphere did not cause anaphylaxis. Therefore, QCMC/OMMT nanocomposites from natural materials are considerably suitable to apply as drug-controlled release carriers.     

Tri-layered chitosan scaffold as a potential skin substitute

A tri-layered chitosan-based scaffold was successfully made to replicate the striation of a full-thickness skin more accurately than a single- or bi-layered scaffold, which needed weeks of co-culturing of fibroblasts and keratinocytes to achieve similar striation. Chitosan solution was freeze-dried and made into porous disks. Chitosan or chitosan–pectin in acetic acid solution was electrospun onto the chitosan disk to form a nanofibrous layer and a thin film. Examinations based on scanning electron spectroscopy showed that the scaffold was composed of a porous layer (2 mm) to simulate the dermis, a thin film (25–45 μm) to mimic the basement membrane, and a layer of nanofibers (100–200 μm) to serve as the protective epidermis. The tensile strength and modulus of the composite scaffold were significantly higher than those of the chitosan disk (p < 0.01). The composite was able to quickly absorb water and stayed intact throughout the course of the 14-day cell culture tests. The fibroblast cells seeded on both sides of the scaffolds were able to proliferate and stayed separated by the thin film.     

Development of chitosan/gelatin hydrogels incorporation of biphasic calcium phosphate nanoparticles for bone tissue engineering

Abstract

The chitosan/gelatin hydrogel incorporated with biphasic calcium phosphate nanoparticles (BCP-NPs) as scaffold (CGB) for bone tissue engineering was reported in this article. Such nanocomposite hydrogels were fabricated by using cycled freeze-thawing method, of which physicochemical and biological properties were regulated by adjusting the weight ratio of chitosan/gelatin/BCP-NPs. The needle-like BCP-NPs were dispersed into composites uniformly, and physically cross-linked with chitosan and gelatin, which were identified via Scanning Electron Microscope (SEM) images and Fourier Transform Infrared Spectroscopy (FT-IR) analysis. The porosity, equilibrium swelling ratio, and compressive strength of CGB scaffolds were mainly influenced by the BCP-NPs concentration. In vitro degradation analysis in simulated body fluids (SBF) displayed that CGB scaffolds were degraded up to at least 30?wt% in one month. Also, CCK-8 analysis confirmed that the prepared scaffolds had a good cytocompatibility through in culturing with bone marrow mesenchymal stem cells (BMSCs). Finally, In vivo animal experiments revealed that new bone tissue was observed inside the scaffolds, and gradually increased with increasing months, when implanted CGB scaffolds into large necrotic lesions of rabbit femoral head. The above results suggested that prepared CGB nanocomposites had the potential to be applied in bone tissue engineering.