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用于肽、蛋白质和核酸药物递送的纳米颗粒系统的研究进展。

Progress in nanoparticulate systems for peptide, proteins and nucleic acid drug delivery.

机构信息

Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland. staslomk@.cbmm.lodz.pl

出版信息

Curr Pharm Biotechnol. 2011 Nov;12(11):1823-39. doi: 10.2174/138920111798377003.

Abstract

Progress in many therapies, in particular in the therapies based on peptides, proteins and nucleic acids used as bioactive compounds, strongly depends on development of appropriate carriers which would be suitable for controlled delivery of the intact abovementioned compounds to required tissues, cells and intracellular compartments. This review presents last ten years' achievements and problems in development and application of synthetic polymer nanoparticulate carriers for oral, pulmonary and nasal delivery routes of oligopeptides and proteins. Whereas some traditional synthetic polymer carriers are only briefly recalled the main attention is concentrated on nanoparticles produced from functional copolymers mostly with hydroxyl, carboxyl and amino groups, suitable for immobilization of targeting moieties and for assuring prolonged circulation of nanoparticles in blood. Formulations of various nanoparticulate systems are described, including solid particles, polymer micelles, nanovesicles and nanogels, especially systems allowing drug release induced by external stimuli. Discussed are properties of these species, in particular stability in buffers and models of body fluids, loading with drugs and with drug models, drug release processes and results of biological studies. There are also discussed systems for gene delivery with special attention devoted to polymers suitable for compacting nucleic acids into nanoparticles as well as the relations between chemical structure of polymer carriers and ability of the latter for crossing cell membranes and for endosomal escape.

摘要

在许多疗法,特别是基于肽、蛋白质和核酸等生物活性化合物的疗法方面取得了进展,这在很大程度上取决于适当载体的发展,这些载体适合将完整的上述化合物受控递送到所需的组织、细胞和细胞内隔室。本综述介绍了过去十年中在开发和应用用于口服、肺部和鼻腔给药途径的寡肽和蛋白质的合成聚合物纳米颗粒载体方面的成就和问题。虽然一些传统的合成聚合物载体仅被简要回顾,但主要关注的是由带有羟基、羧基和氨基的功能共聚物制备的纳米颗粒,这些纳米颗粒适合固定靶向部分,并确保纳米颗粒在血液中的延长循环。描述了各种纳米颗粒系统的制剂,包括固体颗粒、聚合物胶束、纳米囊泡和纳米凝胶,特别是允许外部刺激诱导药物释放的系统。讨论了这些物质的特性,特别是在缓冲液和体液模型中的稳定性、药物和药物模型的负载、药物释放过程以及生物学研究的结果。还讨论了用于基因传递的系统,特别关注适合将核酸压缩成纳米颗粒的聚合物,以及聚合物载体的化学结构与后者穿过细胞膜和内体逃逸的能力之间的关系。

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