Surface-modified Epirubicin-HCl liposomes and its in vitro assessment in breast cancer cell-line: MCF-7

Abstract

Background: Epirubicin-HCl is highly efficient for breast cancer management at a concentration of 60–90 mg/m². However, its application is limited due to cumulative dose-dependent cardio-toxicity.

Purpose: The main aim of this study was to formulate breast cancer-targeted liposomal carrier by surface conjugation of transferrin to minimize cardio-toxicity of drug along with improved pharmacokinetic profile.

Method: Liposomes were formulated by ethanol injection method using HSPC, cholesterol and DSPG and later loaded with drug by the ammonium sulfate gradient method. The formulation was characterized for physicochemical properties like size, zeta potential, entrapment efficiency, TEM; in vitro tests like electro-flocculation, hemolysis and drug release; cell line study (MCF-7 cells); in vivo studies including LD₅₀ determination, pharmacokinetic analysis, myocardial toxicity determination and stability.

Results and discussion: Optimized formulation had molar ratio of 60:30:8:2 (HSPC:Chol:DSPG:mPEG-DSPE) with entrapment efficiency ∼83%, particle size below 200 nm and zeta potential about −20 mV. In vitro studies proved non-interfering property and drug release character of formulation while cell line studies demonstrated improvement in cell uptake and thereby increased cytotoxicity of targeted formulation. The IC₅₀ value obtained for epirubicin solution, non-targeted and targeted liposomes was 0.675, 0.532 and 0.192 µg/ml, respectively. Furthermore, in vivo tests validated safety and distribution profile of prepared formulations.

Conclusion: Apt properties of prepared Epirubicin-HCl liposomal formulation warrant its clinical application in breast cancer treatment after further studies.

• Epirubicin
• liposomes
• pharmacokinetics
• targeted drug delivery
• transferrin

Acknowledgements

Authors would like to acknowledge TIFAC-CORE for providing research facilities and Dr. Vikram Sarabhai Science Block, The M.S. University of Baroda, for providing facilities for cell uptake studies.

Declaration of interest

Authors report no conflict of interests and are responsible for the content of the paper.