High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: Quality by design optimization and characterization
High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: Quality by design optimization and characterization
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DOI：
10.1016/j.ejpb.2010.11.008
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Nielsen, Hanne Morck
中科院分区：
文献类型：
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作者：
Cun, Dongmei;Jensen, Ditte Krohn;Nielsen, Hanne Morck
聚（DL-丙交酯-乙交酯酸）（PLGA）由于其生物相容性、生物降解性和出色的控释特性，是一种极具吸引力的生物药物递送聚合物。本研究的目的是了解和定义通过双乳液溶剂蒸发法制备负载小干扰 RNA (siRNA) 的 PLGA 纳米颗粒的最佳参数并表征其性能。实验按照基于 5 个自变量的 2(5-1) 部分因子设计进行：内部水相和油相之间的体积比、PLGA 浓度、超声处理时间、siRNA 负载以及内部水相中为稳定初级乳液而添加的乙酰化牛血清白蛋白 (Ac-BSA) 的量。研究了对 siRNA 封装效率和粒径的影响。获得高达70%的包封率最重要的因素是PLGA浓度和体积比，而尺寸主要受PLGA浓度影响。油相的粘度在高 PLGA 浓度下增加，这解释了通过稳定初级乳液和减少 siRNA 泄漏到外部水相而改善的封装。添加 Ac-BSA 提高了低 PLGA 浓度下的包封效率。 PLGA 基质保护 siRNA 免受核酸酶降解，提供表面定位 siRNA 的突发释放，然后是三个月的三相持续释放。这些结果使我们能够仔细理解和定义制备封装大量 siRNA 且具有立即和长期持续释放特性的 PLGA 纳米颗粒的最佳工艺参数。 (C) 2010 Elsevier B.V. 保留所有权利。
Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. (C) 2010 Elsevier B.V. All rights reserved.