Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine
Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine
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DOI：
10.1016/j.ijpharm.2006.05.061
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发表时间：
2006-11-06
影响因子：
5.8
通讯作者：
Aminabhavi, Tejraj M.
中科院分区：
文献类型：
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作者：
Agnihotri, Sunil A.;Aminabhavi, Tejraj M.
以戊二醛为交联剂，通过乳液交联法制备了卡培他滨半互穿网络型壳聚糖-聚氧乙烯-丙烯酰胺水凝胶微球。以硝酸铈铵为氧化还原引发剂，采用自由基聚合法将聚环氧乙烷接枝到聚丙烯酰胺上。通过改变接枝共聚物的接枝率、接枝共聚物与壳聚糖的比例、交联剂的用量和载药量等实验变量，对微球的包封率、释放率、大小和形态进行优化，成功地将抗癌药物卡培他滨负载到微球中。采用2(4)全析因设计评价所选自变量对5h释药百分率的综合影响。反应采用回归模型，数据比较采用方差分析(ANOVA)。用傅立叶红外光谱(FTIR)表征了卡培他滨微球的接枝、互穿网络形成和化学稳定性。采用差示扫描量热法(DSC)和X射线衍射法(XRD)对载药微球进行了研究，考察了载药微球包埋后的结晶性质。结果表明，卡培他滨在聚合物基质中呈无定形分散。扫描电子显微镜(SEM)证实微球呈球形，表面形态光滑。激光光散射法测得的微球平均粒径为82~168微米，卡培他滨成功包封半互穿网络微球，包封率为79~87%。体外释放研究在模拟胃液(pH 1.2)中进行，最初2小时，然后是模拟肠液(pH 7.4)，直到完全溶解。卡培他滨的释放持续到10h。释放数据与经验关系进行了拟合，以估计输运参数。在模拟肠液中进行动态溶胀研究，并通过考虑基质的球状几何形状来计算扩散系数。(C)2006爱思唯尔B.V.保留所有权利。
This paper describes the synthesis of capecitabine-loaded semi-interpenetrating network hydrogel microspheres of chitosan-poly(ethylene oxide-g-acrylamide) by emulsion crosslinking using glutaraldehyde. Poly(ethylene oxide) was grafted with polyacrylamide by free radical polymerization using ceric ammonium nitrate as a redox initiator. Capecitabine, an anticancer drug, was successfully loaded into microspheres by changing experimental variables such as grafting ratio of the graft copolymer, ratio of the graft copolymer to chitosan, amount of crosslinking agent and percentage of drug loading in order to optimize process variables on drug encapsulation efficiency, release rates, size and morphology of the microspheres. A 2(4) full factorial design was employed to evaluate the combined effect of selected independent variables on percentage of drug release at 5 h (response). Regression models were used for the response and data were compared statistically using the analysis of variance (ANOVA). Grafting, interpenetrating network formation and chemical stability of the capecitabine after encapsulation into microspheres was confirmed by Fourier infrared spectra (FTIR). Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) studies were made on drug-loaded microspheres to investigate the crystalline nature of drug after encapsulation. Results indicated amorphous dispersion of capecitabine in the polymer matrix. Scanning electron microscope (SEM) confirmed spherical shapes and smooth surface morphology of the microspheres. Mean particle size of the microspheres as measured by the laser light scattering technique ranged between 82 and 168 mu m. Capecitabine was successfully encapsulated into semi-IPN microspheres and percentage of encapsulation efficiency varied from 79 to 87. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2 h, followed by simulated intestinal fluid (pH 7.4) until complete dissolution. The release of capecitabine was continued up to 10h. Release data were fitted to an empirical relationship to estimate the transport parameters. Dynamic swelling studies were performed in the simulated intestinal fluid and diffusion coefficients were calculated by considering the spherical geometry of the matrices. (c) 2006 Elsevier B.V. All rights reserved.