The effect of PEG coating on in vitro cytotoxicity and in vivo disposition of topotecan loaded liposomes in rats

International Journal of Pharmaceutics
S DadashzadehM Rezaie

Abstract

Amphoteric drugs encapsulated in PEGylated liposomes may not show superior therapeutic antitumor activity due to increased leakage rate of these drugs in presence of PEG-lipids. In order to investigate the effect of PEG coating on in vitro and in vivo characteristics of topotecan loaded liposomes, an amphoteric anticancer drug, PEGylated and conventional liposomes were prepared by lipid film hydration method. Various properties of the prepared nanoliposomes such as encapsulation efficiency, size, zeta potential, physical stability as well as the chemical stability of lactone form of topotecan, cytotoxicity and topotecan pharmacokinetics were evaluated. In vitro cytotoxic activity was evaluated on murine Lewis lung carcinoma (LLC) and human mammary adenocarcinoma (BT20) cells. Pharmacokinetic was evaluated in Wistar rats after i.v. injection of topotecan, formulated in PBS pH 7.4 or in conventional or in PEGylated liposomes. The conventional liposome (CL) formulation was composed of DSPC/cholesterol/DSPG (molar ratio; 7:7:3), while for PEGylated liposome the composition was DSPC/cholesterol/DSPG/DSPE-PEG(2000) (molar ratio; 7:7:3:1.28). The size of both liposomes was around 100 nm with polydispersity index of about 0.1. In compa...Continue Reading

Citations

May 23, 2012·Investigational New Drugs·Nilesh A PatankarMarcel B Bally
Aug 31, 2013·International Journal of Nanomedicine·Sai-Ping JiangHong Yuan
Dec 6, 2012·Journal of Liposome Research·Gøril Eide FlatenBeth Goins
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Jan 11, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nilesh A PatankarMarcel B Bally
Nov 19, 2020·International Journal of Nanomedicine·Morteza YaghoobianSimin Dadashzadeh
Oct 25, 2011·International Journal of Biological Macromolecules·Yunpeng FanXiang Ni

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