Formulation and in-vitro characterisation of fulvestrant loaded liposomes for breast cancer therapy

Abstract

Background: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnology strategies for more effective and safer cancer treatment, one of which is liposomes.

Objectives: Considerable technological success has been achieved in this field, but the main obstacles to nano-medicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano–bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization.

Methods: In this study, three different formulations of Fulvestrant liposomes which differ in drug/polymer ratios (A=1:1; B=1:2 and batch C=2:1) were prepared using film hydration technique and thereafter characterized in-vitro by determining the particle sizes, the zeta potentials, drug loading poly dispersible index, drug release profile and the cellular uptake by MCF-7 cell line.

Results: The Fulvestrant liposomes produced were spherical and are of various sizes with average particle size of 191 (d.nm) for formulation A, 760.7 for formulation B and 205.5 (d.nm) formulation C. Formulation B also has the highest drug loading and the poly dispersible index (PDI) values, 30.19 % and 0.750, respectively.The zeta potential values ranged from -14.9mV to -3.40mV for all formulations which suggest relatively stable dispersed liposomal nanoparticle in liquid state. The cumulative drug released for formulation B was 100% and well prolonged for over 1,200 h. Both formulations A and C however did not achieve 100% released of entrapped drug even though the released were equally prolonged and even though the released kinetics for all the three formulations essentially follow the same Korsmeyer mathematical model, as adjudged by the co-efficient of determination values R2. Formulation B was well absorbed in MCF-7 breast cancer cell line and effect time base cytotoxic activity.

Formulation B with Lecithin: Cholesterol ratio of 1:2 showed the highest drug loading, the highest percentage cumulative released of the drug (in a sustained manner for a prolonged period of time) and adequately internalized in the MCF-7 breast cancer cell line in vitro.

Conclusion: Therefore formulation B is more suitable for breast cancer treatment due to its excellent physicochemical characteristics, its good permeation, internalization and the time based killing of the breast cancer cells.

Keywords: Liposome, Nanoparticles, Fulvestrant, Breast cancer