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用于低细胞毒性可生物降解基因递送载体的聚(L-赖氨酸)-g-聚(D,L-乳酸-共-乙醇酸)胶束

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

作者信息

Jeong Ji Hoon, Park Tae Gwan

机构信息

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.

出版信息

J Control Release. 2002 Jul 18;82(1):159-66. doi: 10.1016/s0168-3659(02)00131-1.

Abstract

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.

摘要

合成了聚(乳酸 - 乙醇酸)(PLGA)接枝的聚(L - 赖氨酸)(PLL)(PLL - g - PLGA),以证明其在水溶液中的胶束形成特性。这些胶束用作基因传递载体。PLL - g - PLGA胶束在水溶液中的流体动力学直径约为149 nm,粒径分布较窄。临界胶束浓度(cmc)为9.6 mg/l。PLL - g - PLGA胶束可用于与质粒DNA形成紧密的纳米颗粒复合物,从而有效地保护复合DNA免受DNase I的酶促降解。胶束/DNA复合物具有高度紧密的结构,尺寸在200 - 300 nm之间,表面带正电荷。与PLL相比,PLL - g - PLGA胶束表现出更高的转染效率和更低的细胞毒性。在此,我们证明了可生物降解的阳离子PLL - g - PLGA胶束可作为基因传递系统中有效的DNA凝聚载体。

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