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具有缩醛基团的酸敏性可生物降解聚合物的电纺纤维作为潜在的药物载体。

Electrospun fibers of acid-labile biodegradable polymers with acetal groups as potential drug carriers.

作者信息

Cui Wenguo, Qi Mingbo, Li Xiaohong, Huang Shaozhou, Zhou Shaobing, Weng Jie

机构信息

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.

出版信息

Int J Pharm. 2008 Sep 1;361(1-2):47-55. doi: 10.1016/j.ijpharm.2008.05.005. Epub 2008 May 15.

Abstract

The local delivery and controllable release profiles make electrospun ultrafine fibers as potential implantable drug carriers and functional coatings of medical devices. Till date there is no literature report on drug delivery from acid-labile electrospun fibers, whose degradation and drug release behaviors respond to the local pathological pH environment. Acid-labile groups have been incorporated into nonbiodegradable backbones as crosslinkers or linkers of the side chains. A novel strategy was developed in this study to synthesize acid-labile polymers by introducing acetal groups into biodegradable backbone of poly(dl-lactide)-poly(ethylene glycol). In vitro release study showed that the total amount of drug released from acid-labile polymeric fibers was accelerated on account of pH-induced structural and morphological changes of fibrous mats and the degradation of matrix polymers, and the burst release was significant higher for polymers with higher contents of acid-labile segments. During the investigational period, almost no molecular weight reduction and mass loss was detected in neutral buffer solutions, but the degradation was enhanced in acid buffers with a two-stage degradation profile. Surface erosion mechanism was initially detected for fibrous mats with distinct fiber morphologies, and bulk degradation was determined during the following incubation for polymeric films resulting from the morphological changes.

摘要

局部给药和可控释放特性使电纺超细纤维成为潜在的可植入药物载体和医疗器械的功能涂层。迄今为止,尚无关于酸敏性电纺纤维药物递送的文献报道,其降解和药物释放行为对局部病理pH环境有响应。酸敏基团已被引入不可生物降解的主链中作为侧链的交联剂或连接基。本研究开发了一种新策略,通过将缩醛基团引入聚(dl-丙交酯)-聚(乙二醇)的可生物降解主链中来合成酸敏性聚合物。体外释放研究表明,由于pH诱导的纤维垫结构和形态变化以及基质聚合物的降解,酸敏性聚合物纤维释放的药物总量加速,且酸敏性片段含量较高的聚合物的突释明显更高。在研究期间,在中性缓冲溶液中几乎未检测到分子量降低和质量损失,但在酸性缓冲溶液中降解增强,呈现两阶段降解曲线。对于具有明显纤维形态的纤维垫,最初检测到表面侵蚀机制,而在随后的孵育过程中,由于形态变化导致聚合物膜发生本体降解。

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