Inhibition of drug resistance in ovarian cancer cells (A2780R) by silibinin loaded solid lipid nanoparticles

Abstract

Introduction: Ovarian cancer is the most important cancer in women that cause mortality worldwide. Cisplatin is the main chemotherapeutics that is used in ovarian cancer treatment. Similar to most cancers, taking this drug for a long time causes drug resistance that causes the treatment period to fail. A combination of chemotherapy drugs has been suggested for this problem. Silibinin is a non-toxic natural compound, an extract of silybum marianum seeds. Objective: The aim of this project was to prepare nanostructured lipid carriers (NLC) containing Silibinin (Silibinin-NLC) and to assess its inhibitory effects on the growth of cisplatin-resistant cancer cells by combining Silibinin-NLC and intact cisplatin on ovarian A2780 cells. Method: Silibinin-NLC were prepared by hot homogenization method. Silibinin-NLC were evaluated for size, zeta potential, drug storage, encapsulation efficiency. A2780 cancer cells were cultured and treated with cisplatin and Silibinin-NLC and their combinations, and the cell survival was assessed by MTT assay. Results: Formulation of Silibinin-NLC by hot homogenization method using cocoa butter led to nanoparticles with a size of 95 nm. The encapsulation efficiency of Silibinin-NLC was 98%. The zeta potential of the nanoparticles was -27.12 ± 0.13 mv. The dispersion index of Silibinin-NLC was calculated 0.12 ± 0.04 mv. The release kinetics of the drug was based on the zero order model. SEM results revealed spherical particles. Inhibition of cell growth observed in A2789 cells treated with the combination of cisplatin and Silibinin-NLC was greater than that of the combination of cisplatin and intact Silibinin . The physical stability studies showed that no significant change was observed in drug storage and size of nanocarriers (P> 0.05) Conclusion: NLC can be considered as a suitable drug delivery system for Silibinin