Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy

Drug Delivery
Wenli ZhangJianping Liu

Abstract

To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as 'micelle pool' drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-lo...Continue Reading

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Citations

Dec 6, 2018·Nanomedicine·Gangliang Huang, Hualiang Huang
Aug 31, 2019·Future Medicinal Chemistry·Shiyu Huang, Gangliang Huang
Aug 13, 2020·Drug Delivery and Translational Research·Xuefei LiXianggen Wu
Jan 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhenjiang ZhangMichael R King
Jan 25, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ya JinWenli Zhang

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Methods Mentioned

BETA
dynamic light scattering
fluorescence imaging

Software Mentioned

GraphPad Prism
WinNonlin

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