Development and in vitro characterization of docetaxel-loaded ligand appended solid fat nanoemulsions for potential use in breast cancer therapy.

Context: Breast cancer accounts for 23% of all newly occurring cancers in women worldwide and represents 13.7% of all cancer deaths. Available chemotherapeutic agents are limited largely due to the low accumulation of chemotherapeutics at the tumors relative to their accumulation at normal (healthy) organs due to developed multidrug resistance (MDR) which translates into increased toxicities.

Objectives: To enhance the anticancer potency of docetaxel (DTX), by encapsulating it inside the nanosize lipid particles (folate-conjugated PEG-solid fat nanoemulsions) stabilized by soya phosphatidylcholine (PC) for targeting folate receptors in breast cancer.

Materials And Methods: Tristearin and soya PC-based solid fat nanoemulsions were prepared by cast film technique followed by sonication and modified by coating them with folate receptor-specific ligand (folate-PEG-cholesterol). The surface modified solid fat nanoemulsions and their plain counterparts were characterized for size, shape, lamellarity, zeta potential and entrapment efficiency using scanning electron microscopy, zetasizer and minicolumn centrifugation. The in vitro release profile (dialysis bag technique) and in vitro cytotoxicity (MTT assay) of the developed formulations were evaluated.

Results: The TEM photograph showed homogenous and spherical nature of the particles. The IC50 values of docetaxel solution, plain solid fat nanoemulsions, and folate-conjugated PEG-solid fat nanoemulsions were found to be 14.2, 64.9, and 28.8 μM/ml, respectively. Strong fluorescence was observed in the HeLa cells treated with folate-conjugated PEG-solid fat nanoemulsions which showed higher cellular uptake of ligand-appended solid fat nanoemulsions than plain solid fat nanoemulsions.

Discussion And Conclusion: The results indicated that folate was effective in promoting the internalization of solid fat nanoemulsions encapsulating DTX to the folate receptor-positive tumor cells. This opens the new possibility for non-immunogenic, site-specific delivery of bioactive(s).