A folate receptor-targeted emulsion formulation for paclitaxel

Abstract

Purpose: This study was aimed at the formulation and an in vitro evaluation of folate receptor (FR)-targeted emulsions as carriers for the lipophilic drug paclitaxel, in FR-overexpressing tumor cells.

Materials and methods: FR-targeted paclitaxel emulsions (< 100 nm) composed of Tween-80:triolein:cholesterol:oleic acid:egg-phosphatidylcholine (EPC) (10:30:19.5:30:10), with 0.5 mole % of folate-polyethyleneglycol-cholesterol or polyethyleneglycol-distearoylphosphatidylethanolamine (PEG-DSPE), were prepared by ethanol injection method. Stability of the emulsions was monitored by changes in particle size while at 4 degrees C and 25 degrees C, and drug retention at various time-points. IC50 of the FR-targeted formulations was determined in vitro in the FR+ KB cells.

Results: Stable targeted emulsions were prepared by ethanol injection encapsulating greater than 70 percent of paclitaxel, having a mean diameter < 100 nm. In vitro cytotoxicity assay on the FR-targeted emulsions gave IC50 of 0.13 microM in KB cells. There was a significant difference in the IC50 values between the targeted emulsions and those that were non-targeted.

Conclusion: FR-targeted emulsions incorporating the lipophilic drug paclitaxel were capable of specific receptor binding in cultured KB cells and warrant further investigation in vivo. This article is the first report on an FR-targeted emulsion-type drug carrier. Furthermore, a novel mechanism for in vivo antitumor activity of nanoparticular formulations, such as these emulsions, that is based on their antiangiogenic effect is proposed.