奥曲肽靶向阿霉素脂质体的制备及其体外性质
Preparation and in vitro characterization of octreotide-targeting doxorubicin liposome
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摘要: 探讨奥曲肽靶向脂质体的制备方法。首先采用乙醇注入法和硫酸铵梯度载药法制备阿霉素普通脂质体(P-L)，单因素研究多种处方组成及工艺参数对脂质体性质的影响。随后在阿霉素脂质体表面插入奥曲肽-聚乙二醇4000-氢化磷脂酰乙醇胺（Octreotide- PEG4000 -HSPE），获得奥曲肽靶向阿霉素脂质体(Oct-L)。采用柱分离法和粒径仪考察脂质体包封率、粒径分布、稳定性，透射电镜观察脂质体形态，透析法测定其释放性质。所制备的奥曲肽靶向脂质体外形圆整，粒径略小于100 nm，药物包封率约100%，48 h释放约20%；与阿霉素普通脂质体相比，提高了对生长抑素受体表达阳性的NCI H-446细胞的毒性及其阿霉素摄取量。本实验表明，乙醇注入、硫酸铵梯度及后插入法可应用于阿霉素脂质体的制备及脂质体奥曲肽靶向的修饰。Abstract: The aim of this study was to develop the preparation method of octreotide-targeting doxorubicin liposome.First,doxorubicin plain liposome (P-L) was prepared by ethanol injection and ammonium sulfate gradient loading,and optimized by single-factor design regarding formulation and pharmaceutical process.Then octreotide-targeting liposome (Oct-L) was obtained by post-inserting Octreotide-PEG4000-HSPE into prepared liposome.Sephadex G-50 column separation and zetasizer were used to evaluate drug entrapment efficiency,size distribution and storage stability; transmission electron microscopy was used to evaluate its surface morphology and dialysis method was used to investigate the drug release profile.It was shown that octreotide-targeting liposome had a mean size of 100 nm and a drug entrapment efficiency of 100%.The liposome particle was round and only 20% of entrapped doxorubicin was released after 48h incubation in pH 7.4 PBS under 37 °C.Compared to plain doxorubicin liposome,octreotide-targeting doxorubicin liposome showed stronger cytotoxicity and higher cellular uptake on NCI H-446 expressing somatostatin receptor.Therefore,ethanol injection,ammonium sulfate gradient loading and post-insertion method can be utilized to construct doxorubicin liposome and to achieve octreotide targeting modification.
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