两亲性壳聚糖衍生物负载及缓释醋酸曲安奈德的性能

背景：醋酸曲安奈德是一种长效肾上腺糖皮质激素，具有较强的抗炎作用。近年来在眼内疾病的治疗中取得了较好的效果，但同时带来一些不良反应，且需多次注射，以防止疾病复发。壳聚糖经接枝改性，生成的共聚物可在水溶液中生成纳米粒，用于药物的缓释载体，延长药物作用时间，降低不良反应，提高生物利用度。 目的：合成含脱氧胆酸基团的两亲性壳聚糖衍生物作为醋酸曲安奈德的载体材料，制备具有缓释功能的载药纳米胶束，研究其负载和缓释醋酸曲安奈德的性能。 方法：通过酰胺化反应在壳聚糖上偶联脱氧胆酸基团，合成两亲性壳聚糖衍生物。透射电镜观察纳米粒的外观形态和粒径，Zeta电位分析仪测定纳米粒的Zeta电位，体外释放实验检测负载醋酸曲安奈德的壳聚糖-脱氧胆酸纳米粒的包封率、载药量和体外释药性能。 结果与结论：合成出含脱氧胆酸基团的两亲性壳聚糖衍生物，它能与醋酸曲安奈德形成载药纳米胶束，载药量可高达82%。随着载药量的增加，载药纳米胶束的粒径逐渐增大，而Zeta电位则呈下降的趋势。体外释放的结果表明载药纳米胶束能起到72 h缓释醋酸曲安奈德的作用。提示以两亲性壳聚糖衍生物为载体的载药纳米胶束显示出较好的缓释醋酸曲安奈德性能，将有希望提高醋酸曲安奈德的治疗效果。 关键词：醋酸曲安奈德；两亲性壳聚糖衍生物；脱氧胆酸；纳米胶束；体外药物释放 doi:10.3969/j.issn.1673-8225.2010.29.013

Bioloading of amphiphilic chitosan derivatives and their sustained-release of triamcinolone acetonide acetate

BACKGROUND: Triamcinolone acetonide acetate (TAA) has strong anti-inflammatory effects as a long-acting corticosteroid. TAA has shown good results in the treatment of intraocular diseases in recent years, however, it also brings some side effects, and needs multiple injections to prevent disease recurring. Grafted chitosan, a copolymer, can generate nanoparticles in aqueous solution, and can be used as a drug carrier for extending the duration of drugs, reducing its side effects and improving its bioavailability. OBJECTIVE: To synthesize the amphiphilic chitosan derivative containing deoxycholic acid groups and to use it as a carrier to encapsulate TAA, to prepare drug-loading nanoparticles of sustained-release function, and to study the load and performance of sustained-release TAA. METHODS: The amphiphilic chitosan derivative was synthesized through amidation reaction. Morphology and particle size of nanoparticles were observed by transmission electron microscopy, Zeta potential of nanoparticles was measured by Zeta potential analyzer. The entrapment efficiency, drug loading and in vitro drug release properties of TAA-loaded chitosan-deoxycholic acid nanoparticles were determined by in vitro release assay. RESULTS AND CONCLUSION: The synthesized amphiphilic chitosan derivatives containing TAA could form drug-loaded nanoparticles, of which drug loading content was 82%. With the increasing drug loading content, the particle sizes of drug-loaded nanoparticles increased, while their Zeta potential values decreased. The result of in vitro release assay indicated that the drug-loaded nanoparticles constantly released TAA in a sustained manner within 72 hours. The drug-loaded nanoparticles based on the amphiphilic chitosan derivative exhibited a sustained-release behavior and is potential to increase the therapeutic effect of TAA.