Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage
Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage
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DOI：
10.1016/j.ejpb.2009.02.002
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Langer, Klaus
中科院分区：
文献类型：
--
作者：
Holzer, Melisande;Vogel, Vitali;Langer, Klaus
纳米颗粒是一种很有前途的药物控释载体。颗粒的大小和分布是静脉注射后体内行为的重要参数，必须进行精确的表征。本文研究了冷冻干燥对几种冷冻保护剂配制的聚(D，L)乳酸-乙醇酸共聚纳米粒(PLGA)储存稳定性的影响。采用高压溶剂挥发法制备纳米颗粒，分别在1%、2%和3%(m/v)的蔗糖、海藻糖和甘露醇存在下冷冻干燥。此外，在所有含有3%辅料的样品中，加入浓度为2.1%或8.4%(m/V)的L精氨酸盐酸盐。采用动态光散射(DLS)、分析超速离心法和透射电子显微镜(TEM)对冻干前后的颗粒进行了表征。另外，用差示扫描量热法(DSC)测定了冻干剂的玻璃化转变温度，用卡尔-费休法分析了冻干剂的残留水分。结果表明，1%的蔗糖或2%的海藻糖适合于冻干PLGA纳米粒的重组后保持粒子的完整性。3个月的储存稳定性研究表明，根据配方组成的不同，平均颗粒尺寸、粒度分布和残余水分含量都发生了显著变化。(C)2009爱思唯尔B.V.保留所有权利。
Nanoparticles represent promising carriers for controlled drug delivery. Particle size and size distribution of the particles are important parameters for the in vivo behaviour after intravenous injection and have to be characterised precisely. In the present study, the influence of lyophilisation on the storage stability of poly(D,L lactic-co-glycolic acid) (PLGA) nanoparticles, formulated with several cryoprotective agents, was evaluated. Nanoparticles were prepared by a high pressure solvent evaporation method and freeze-dried in the presence of 1%, 2%, and 3% (m/v) sucrose, trehalose, and mannitol, respectively. Additionally, to all samples containing 3% of the excipients, L-arginine hydrochloride was added in concentrations of 2.1% or 8.4% (m/V). Dynamic light scattering (DLS), analytical ultracentrifugation and transmission electron microscopy (TEM) were used for particle characterisation before and after freeze-drying and subsequent reconstitution. In addition, glass transition temperatures were determined by differential scanning calorimetry (DSC), and the residual moisture of the lyophilisates was analysed by Karl Fischer titration. It was demonstrated that 1% sucrose or 2% trehalose were suitable to maintain particle integrity after reconstitution of lyophilised PLGA nanoparticles. The storage stability study over 3 months showed notable changes in mean particle size, size distribution, and residual moisture content, depending on the composition of the formulation. (C) 2009 Elsevier B.V. All rights reserved.