乙二醇
药物输送
卵磷脂
材料科学
PEG比率
PLGA公司
生物相容性
纳米颗粒
脂质体
细胞毒性
纳米技术
可生物降解聚合物
纳米医学
控制释放
毒品携带者
化学工程
化学
聚合物
色谱法
有机化学
体外
生物化学
财务
经济
冶金
复合材料
工程类
作者
Juliana M. Chan,Liangfang Zhang,Kai P. Yuet,Grace Liao,June‐Wha Rhee,Róbert Langer,Omid C. Farokhzad
出处
期刊:Biomaterials
[Elsevier]
日期:2009-03-01
卷期号:30 (8): 1627-1634
被引量:615
标识
DOI:10.1016/j.biomaterials.2008.12.013
摘要
Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.
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