Preparation and characterization of venlafaxine hydrochloride‐loaded chitosan nanoparticles and in vitro release of drug

The venlafaxine hydrochloride (VHL)‐loaded chitosan nanoparticles were prepared by ionic gelation of chitosan (CS) using tripolyphosphate (TPP). The nanoparticles were characterized using FTIR, differential scanning calorimetry, X‐ray diffraction, dynamic light scattering, transmission electron microscopy, and X‐ray photoelectron spectroscopy. The effect of concentration of CS, polyethylene glycol (PEG), VHL and CS/TPP mass ratio on the particle size and zeta potential of nanoparticles was examined. The particle size of CS/TPP nanoparticles and VHL‐loaded CS/TPP nanoparticles was within the range of 200–400 nm with positive surface charge. In the case of VHL‐loaded nanoparticles and PEG‐coated CS/TPP nanoparticles, the particle size increases and surface charge decreases with increasing concentration of VHL and PEG. Both placebo and VHL‐loaded CS/TPP nanoparticles were observed to be spherical in nature. PEG coating on the surface of CS/TPP nanoparticles was confirmed by XPS analysis. Maximum drug entrapment efficiency (70%) was observed at 0.6 mg/mL drug concentration. In vitro drug release study at 37°C ± 0.5°C and pH 7.4 exhibited initial burst release followed by a steady release. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and blood compatibility of phosphorylcholine‐bonded O‐butyrylchitosan

2‐Methacryloyloxyethyl phosphorylcholine (MPCE) was synthesized using phosphorus trichloride, ethylene glycol, 2‐hydroxyethyl methacrylate and triethylamine, and then used in the preparation of O‐butyrylchitosan‐bonded MPCE (MPCE–BCS) by Michael addition of MPCE to amino groups of O‐butyrylchitosan. The structures of MPCE and MPCE–BCS were characterized by FTIR and ¹H NMR. The blood‐compatibility of MPCE–BCS was evaluated by means of blood clotting and platelet adhesion assays. The blood‐clotting assay indicated that O‐butyrylchitosan was haemocompatible. Both the blood‐clotting assay and platelet adhesion assay confirmed that MPCE–BCS had excellent antithrombogenicity. © 2003 Society of Chemical Industry     

Preparation,characterization, and swelling and drug release properties of a crosslinked chitosan‐polycaprolactone gel

For applications in biotechnology to prepare biopolymers containing functional groups is essential. In addition, these materials have to be strong to provide physical support for practical applications. Recently, chitosan, polycaprolactone (PCL), and their various combinations were used for this purpose. In this work, we described the preparation and characterization of a new biodegradable polymeric gel containing chitosan and PCL. The gel preparation reactions were performed in suitable acetic acid solutions to obtain the products in high yields. A crosslinking agent was added to produce crosslinked gels. Swelling behavior of chitosan/PCL gels in different compositions was studied, and the results were compared. The chitosan/PCL gels show a rather large equilibrium swelling in water and in the phosphate buffered saline solution. Acrylic acid (AA) was added to these gels during preparation process to obtain a stable material for various applications. These polymeric gels were characterized by Fourier transform infrared. Their physical and morphological properties were investigated by using differential scanning calorimeter and scanning electron microscope techniques, respectively. Cell growth experiments indicate that chitosan, a positively charged polysaccharide, is not suitable for cell proliferation studies. On the other hand, the drug release studies were successful and, 59% of lidocaine, was released from a chitosan/PCL/AA hydrogel in buffer solution at pH = 7.4 at 37°C. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

This paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.     

Preparation,characterization, and protein loading properties of N‐acyl chitosan nanoparticles

Various N‐acyl chitosans with propionyl‐, hexanoyl‐, nonanoyl‐, lauroyl‐, pentadecanoyl‐, and stearoyl‐groups were synthesized and self‐aggregated N‐acyl chitosan nanoparticles (CSNPs) were prepared by sonication. By the modification with N‐acyl groups, CSNPs increased their hydrophobic character and changed its structural features to be more suitable as a delivery carrier. The mean diameters of bovine serum albumin (BSA)‐loaded N‐acyl CSNPs ranged from 138 to 551 nm. Uniform particle size distribution of BSA‐loaded N‐acyl CSNPs was observed. The protein loading efficiency of N‐acyl CSNPs was about 94–95% with lower BSA concentration (0.1 mg/mL) and not significantly different with acyl chain length. With higher BSA concentration (1.0 mg/mL), however, the highest protein loading efficiency was observed with lauroyl and pentadecanoyl CSNPs. The results suggest that lauroyl and pentadecanoyl CSs are interesting candidates for protein delivery system. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation,characterization and release profiles of pH‐sensitive chitosan beads

Spherical crosslinked beads using chitosan, glycine and glutaraldehyde were prepared for controlled release formulations. Structural investigation of the beads was made with IR analysis. Morphological study of the beads was carried out by scanning electron microscopy. The swelling behaviour of the beads was monitored as a function of time in solutions of different pH. The release experiments were performed using thiamine hydrochloride (Thi‐HCl) as a model drug. These preliminary results suggest the possibility of modifying the formulations to obtain the desired controlled release of drug in an oral sustained delivery system. © 2000 Society of Chemical Industry     

Glutaraldehyde‐crosslinked chitosan beads for controlled release of diclofenac sodium

An inexpensive and simple method was adopted for the preparation of chitosan beads, crosslinked with glutaraldehyde (GA), for the controlled release of diclofenac sodium (DS). The beads were prepared by varying the experimental conditions such as pH, temperature, and extent of crosslinking. The absence of any chemical interaction among drug, polymer, and the crosslinking agent was confirmed by FTIR and thermal analysis. The beads were characterized by microscopy, which indicated that the particles were in the size range of 500–700 μm and SEM studies revealed smooth surface and spherical shape of beads. The beads produced at higher temperature and extended exposure to GA exhibited lower drug content, whereas increased drug loading resulted in enhanced drug release. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 211–217, 2007     

Kinetics of in vitro drug release from chitosan/gelatin hybrid membranes

In vitro studies of controlled release from chitosan/gelatin hybrid membranes were carried out using drugs of different molecular weight. It was found that release of urea, 5-fluorouracil (5-Fu), sodium benzoate, sodium salicylate, sodium mandelate, and sulfacetamide sodium followed zero-order kinetics after a short time lag. Variation of the diffusion coefficient, permeation coefficient, and degree of hydration with crosslinking and varying weight percent of gelatin in membrane matrices were studied in detail by using 5-Fu as a model drug. The diffusion coefficient and permeation coefficient of 5-Fu are dependent on the degree of hydration of the swollen membrane. The transport process of drug molecules in the hydrogel membrane is presumed to be predominantly of the pore mechanism. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1751–1758, 1998     

N-mPEG-O-季铵化壳聚糖微球的制备及其载药性能

将聚乙二醇单甲醚（mPEG）醛化改性后,通过西佛碱反应接枝到自制的O-季铵化壳聚糖的NH2上,硼氢化钠还原制得N-mPEG接枝O-季铵化壳聚糖（QACS-mPEG）,反相悬浮法制备二乙烯基砜交联QACS-mPEG微球。用FTIR、1 H NMR、EA和SEM对产物进行表征,并且以酮洛芬为模型药物研究微球的载药性能及释放行为。结果表明,mPEG和季铵盐基团的引入提高了N-mPEG-O-季铵化壳聚糖微球的载药量,为4.31mg/mg;载药N-mPEG-O-季铵化壳聚糖微球在模拟肠液的缓释效果优于胃液,微球释药具有pH响应性。     

载阿霉素聚乳酸多孔微球的表征及释药性能

以阿霉素（DOX）为小分子化学药物模型,采用吸附法对聚乳酸（poly-L-lactide,PLLA）多孔微球进行载药,采用场发射扫描电子显微镜（FE-SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRPD）及差示扫描量热（DSC）对DOX-PLLA复合微球的形貌粒径及空气动力学性能、药物及材料的理化性能、载药性能进行表征,并且研究了其载药量、包封率和体外释放性能。结果表明,不同载药量之间的PLLA多孔微球粒径并无显著差异,均具有良好的空气动力学性能,适合肺部可吸入给药的条件;化学组成未见明显改变,物理结构由结晶态变为无定形态;随载药量的增加（2.9%,4.0%,4.6%）,包封率逐渐降低（56%,51%,44%）;药物的体外释放与原料药相比具有一定的缓释效果,最长释放时间可达5天,表明DOX-PLLA复合微球有望作为缓释制剂用于肺部给药。     

Dual-drug delivery of sodium ceftriaxone and metronidazole by applying salt-assisted chitosan nanoparticles: Stability,drug release,and time-kill assay study against Bacteroides fragilis

The purpose of this study was to develop a polymeric biomaterial with regulated dual drug release and increased bactericidal strength of the antibiotics sodium ceftriaxone (CTX) and metronidazole (MTZ) for the treatment of intra-abdominal infections. Chitosan nanoparticles (CS NPs) were produced by ionic crosslinking process in the presence of NaCl monovalence salt. The antibacterial activity and drug release behavior of CS NPs were investigated against anaerobic Bacteroides fragilis. The optimum initial drug ratio for designing dual drug carriers containing CTX and MTZ in a 4:3 ratio was 1:1. After 6 months, the salt-assisted CTX-MTZ-loaded CS NPs were 300 nm in size and had a polydispersity index of 0.09 with high stability. It has been demonstrated that drug release from NPs is more tightly controlled than drug release from free drugs. Furthermore, the data show that the minimum inhibitory concentration and minimum bactericidal concentration for nanostructure carriers are one-quarter of those of free medicines. Free drugs could completely kill the bacterium after 24 h, but the dual drug carrier could kill the bacteria in 10 h. Finally, salt-assisted CTX-MTZ-loaded CS NPs were proposed as a feasible alternative to standard intra-abdominal infection treatment.     

Preparation of poly(ethylene glycol)/chitosan membranes by a glucose‐mediating process and in vitro drug release

Novel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005     

Characterization of gamma irradiated concentrated aqueous solutions of chitosan/sodium alginate blends and their drug uptake‐release characters

Blends films based on different ratios of concentrated aqueous solutions of chitosan (CS) and sodium alginate (AG) in the presence of 1% of glutaraldehyde, as a cross‐linking agent for chitosan, were prepared by solution casting and then exposed to gamma irradiation. The formed blends were characterized by IR spectroscopic analysis, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The uptake‐release properties of CS/AG blends, taking ketoprofen as an example for drug, were also investigated. DSC thermograms of CS/AG blends revealed good miscibility was sustained between CS and AG. The water uptake and gel content of CS/AG blends was found to decrease by increasing the ratio of AG in the initial solution. The IR spectra indicated the formation of cross‐linking and hydrogen bonding, while the TGA study showed that the CS/AG blends displayed higher thermal stability than pure CS polymer. Based on Fick's law, it was demonstrated that the main parameters affecting the release of ketoprofen drug from the CS/AG blend hydrogels were composition and pH. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

“类乒乓球”状壳聚糖微球对环丙沙星的控制释放性能的研究

以甲醛作为交联剂,通过悬浮交联法得到单分散性的微米级微球。采用分光光度法研究了壳聚糖微球对环丙沙星的载药释药性能,考察了环丙沙星初始浓度、pH、微球粒径大小、载药时间及温度对饱和吸附量的影响。结果表明,在初始浓度为200 mg/L,pH为8.80和时间为65 min,温度为37℃的优化条件下,壳聚糖微球对环丙沙星的载药量最大,最大吸附量为325 mg/g。在pH为7.4,温度为37℃的模拟人体肠胃缓冲溶液(NaH2PO4/NaOH)中研究了初始浓度以及释放时间对释放结果的影响。实验表明,环丙沙星在担载时与环丙沙星的初始浓度有关,浓度越大,担载量越大,但是担载效率和浓度之间无确定的线性关系。在环丙沙星释放初期有明显的释放现象,但是随着时间的推移,药物释放逐渐稳定,释药效率可达97%左右。     

Synthesis,characterization, and antimicrobial activity of chitosan hydrazide derivative

A series of modified chitosan derivatives 1–4 has been synthesized. Modification process of chitosan was achieved through a sequence of four reactions starting by protection of its amino group with benzaldehyde (derivative 1), followed by reaction with epichlorohydrine (derivative 2), then reaction with benzhydrazide (derivative 3), and finally restoring the free amino groups on the chitosan by removing of benzaldehyde molecules (derivative 4). These four derivatives were characterized by elemental analyses, FTIR, and X-ray. The four chitosan derivatives showed better antibacterial and antifungal activities than that of chitosan. Derivative 4 exhibited the highest antimicrobial activity relative to the other derivatives.     

Chitosan and chitosan/β‐cyclodextrin microspheres as sustained‐release drug carriers

The main aim of this study was to compare two microspheres, chitosan (CTS) and CTS/β‐cyclodextrin (β‐CD), made by spray‐drying, as pulmonary sustained drug‐delivery carriers. Theophylline (TH) was used as a model drug. The characteristics of the microspheres and in vitro release were studied. The yield of CTS/β‐CD microspheres was 46.1%, which was higher than that of the CTS microspheres (36.5%). The drug loads of the CTS and CTS/β‐CD microspheres were 22.7 and 21.1%, respectively, whereas the encapsulation efficiencies were 90.7 and 91.4%, respectively. The distribution of 50% [(diameter) d (0.5)] of the CTS microspheres was below 6.49 μm and that of the CTS/β‐CD microspheres was below 4.90 μm. Scanning electron microscopy showed that both microspheres yielded a spherical shape with smooth or wrinkled surfaces. Fourier transform infrared spectroscopy demonstrated that the carbonyl group of TH formed hydrogen bonds with the amide group of CTS and the hydroxyl group of β‐CD. The swelling ability of the two microspheres was more than three times their weight, and their humidity rates attained equilibrium within 24 h. The ciliary beat movement times of CTS and CTS/β‐CD microspheres were 493.00 and 512.33 min, respectively, which indicated that the two microspheres effectively reduced the ciliotoxicity and possessed better adaptability. In vitro release of TH from CTS/β‐CD microspheres was slower than that from CTS microspheres at pH 6.8 and provided a sustained release of 72.0% within 12 h. The results suggest that CTS/β‐CD microspheres are a promising carrier for sustained release for pulmonary delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1183–1190, 2007     

Gentamicin‐loaded poly(acrylic acid)‐grafted cotton fibers,part 1: Synthesis,characterization, and preliminary drug release study

This study describes preparation of poly (acrylic acid)‐grafted cotton fibers and release of antibiotic drug gentamicin sulfate from them under physiological conditions. Poly(acrylic acid) has been grafted onto cellulose backbone of cotton fibers via Ce(IV)‐initiated polymerization in aqueous medium. The conditions obtained for optimum grafting were as follows: initiation time 30 min; initiation temperature 37°C; monomer concentration 27.8 mM; grafting temperature 30°C; nitric acid (catalyst) concentration 0.1M. The grafted fibers were characterized by FTIR, TGA, and SEM analysis. The antibiotic drug gentamicin sulfate (GS) was loaded into the grafted fibers by equilibration method and release was studied under physiological conditions. The kinetic release data was interpreted by first‐order kinetic model. Finally, drug‐loaded fibers showed fair antibacterial action against Escherichia coli. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and anticoagulant property of phosphorylcholine‐terminated o‐benzoylchitosan derivative

To improve the solubility in organic solvent of chitosan, o‐benzoylchitosan was synthesized by acylation with benzoyl chloride and then used in the reaction with 2‐chloro‐1,3,2‐dioxaphosphospholane (COP) to prepare phosphorylcholine‐terminated o‐benzoylchitosan (PC‐BCS). PC‐BCS had a structure with a phospholipid polar group characterized by FTIR and ¹H NMR. PC‐BCS had been polysubstituted by a PC group, which made PC‐BCS viscous liquid. The anticoagulant properties of PC‐BCS were evaluated by means of blood‐clotting and platelet adhesion assay. The blood‐clotting assay indicated that PC‐BCS could prolong the blood‐clotting process. Platelet adhesion assay showed that PC‐BCS could effectively inhibit the platelet adhesion and activation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 489–493, 2003     

Synthesis of dextran‐metaxalone conjugates and study on their control drug release behaviors

Metaxalone (Met), a drug for treatment of pain and stiffness due to muscle injuries, was covalently linked to dextran via a chloroacetyl chloride spacer. The average molecular weights of dextran are 20,000 (D₂₀₀₀₀) and 40,000 (D₄₀₀₀₀), respectively, and the procedure of chemical modification for dextrans was conducted by a two‐step protocol: (1) synthesis of N‐chloroacetyl‐metaxalone; (2) synthesis of D₂₀₀₀₀‐Met and D₄₀₀₀₀‐Met. The controlled drug release studies were performed in buffer solutions with pH values of 1.1, 7.4, and 10.0. The results demonstrate that, under the same condition, the rate of release for D₂₀₀₀₀‐Met is slower than that of D₄₀₀₀₀‐Met, and more amount of Met can be detected releasing from polymer‐drug conjugate at the presence of α‐chymotrypsin in a buffer solution with pH = 8.0. It was also found that these novel polymer‐drug conjugates can effectively improve the Met's pharmacokinetics, and can increase its half‐life period. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation,evaluation, and in vitro release study of O‐carboxymethyl chitosan nanoparticles loaded with gentamicin and salicylic acid

To inhibit the ototoxicity of gentamicin (GM) and overcome the drawback related to chitosan (CS) nanoparticles preparation in acid solution, O‐carboxymethyl chitosan (O‐CMC) nanoparticles loaded with GM and salicylic acid (SA) were prepared by ionic cross‐linking method using calcium chloride as crosslinking agent. The Fourier transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) were used to analyze the reaction of O‐CMC and crosslinking agent. The parameters of preparation of the compound nanoparticles including the concentration of O‐CMC, the mass ratio of O‐CMC to calcium chloride, and the feed ratio of SA to GM were investigated. The results showed that the obtained nanoparticles had a high zeta potential and drug‐loading capacity. The nanoparticles were characterized by a spherical morphology, with average size ranging from 148 to 345 nm and a narrow particle size distribution. In vitro release studies in phosphate buffer saline (pH 7.4) evidenced a burst release in the first 1 h, followed by a sustained release in the residual time. The release amount of SA and GM were approximately equal in 24 h, which indicated that the SA‐ and GM‐loaded O‐CMC nanoparticles are a promising carrier system for inhibiting the ototoxicity of GM. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012