EGFR-targeted immunoliposomes as a selective delivery system of simvastatin, with potential use in treatment of triple-negative breast cancers

Publication date: Available online 7 August 2019Source: International Journal of PharmaceuticsAuthor(s): Lucyna Matusewicz, Beata Filip-Psurska, Mateusz Psurski, Sabina Tabaczar, Joanna Podkalicka, Joanna Wietrzyk, Piotr Ziółkowski, Aleksander Czogalla, Aleksander F. SikorskiAbstractA promising strategy for treatment of EGFR-dependent tumours is EGFR signal transduction suppression via inhibition of HMG-CoA reductase using high doses of statins, popular cholesterol-lowering drugs.The main purpose of this study was to obtain (tLCLS) with anti-EGFR antibody attached to their surface and to test whether they can be effective in treatment of TNBC. The designed tLCLS were characterized in terms of physicochemical properties and long-term stability. In vitro experiments conducted on MDA-MB-231 cells demonstrated that tLCLS induced apoptosis and are characterized by IC50 of 7.5 µM. Treatment of studied cells with tLCLS led to a decrease in membrane order and inhibited PI3K/Akt signalling. Analyses of efficacy of the tLCLS in in vivo experiments in model animals indicate that immunoliposomes were effectively delivered to tumours. Our results showed that regardless of whether tLCLS were administered before or after tumour formation, at the tested dose they inhibited tumour growth by an average of 25% in comparison to the control. However, the results were not statistically significant.The experiments described above allowed us to test the possibility of using immunoliposomes as sim...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research