Terpene-loaded Liposomes and Isopropyl Myristate as Chemical Permeation Enhancers Toward Liposomal Gene Delivery in Lung Cancer cells; A Comparative Study.

Abstract

Gene therapy is in its development stage as a novel method for cancer treatment. Liposomes look promising as gene delivery vectors; however, investigations have shown that these vesicles are not doing well in some cases. It was decided here to investigate the possibility of augmentation of liposomal gene delivery by chemical penetration enhancers. Cationic liposome containing antisense oligonucleotide (AsODN) against lung cancer was prepared by ethanol injection method. Liposomal cineole and limonene (as enhancers) were prepared by film hydration method. Isopropyl myristate (IPM) was also investigated as penetration enhancer. Liposomes were evaluated for their size, zeta potential and encapsulation efficiency. Cancer cells (A549) were pretreated with liposomal terpenes prior to treatment with liposomal antisense or scrambled oligonucleotide. Cell viability was evaluated by MTT assay. Oligonucleotide -containing liposome showed particle size of about115 nm and zeta potential of 0.6 mV. Liposomal cineole significantly (P<0.05) increased specific activity of liposomal antisense but limonene didn't show such an effect. IPM increased both specific and non-specific cytotoxicity of Oligonucleotide. These results show that penetration enhancers (such as cineole) may be used for improving liposomal gene delivery and to reduce non-specific toxicity. Concentration and chemical nature of enhancer has prominent effect in their efficacy.