Formulation and Evaluation of Self-Emulsifying Drug Delivery Systems of Larotaxel for Oral Administration

Abstract

The objective of the present study was to develop a self-emulsifying drug delivery system of larotaxel and evaluate its in vitro and in vivo performance. The prepared larotaxel loaded self-emulsifying drug delivery system spontaneously formed microemulsion with a mean particle size of 115.4 nm when mixed with 100-fold water under gentle agitation. In vivo pharmacokinetics study of larotaxel loaded self-emulsifying drug delivery system demonstrated 5.19-fold enhancement in oral bioavailability compared to larotaxel-Sol. Furthermore, intestinal bio-distribution studies revealed that the intestinal residence time of larotaxel loaded self-emulsifying drug delivery system was dramatically extended in comparison to larotaxel-Sol. Lymphatic transport studies showed that cycloheximide, a chylomicron secretion blocker, would impede oral absorption of larotaxel loaded self-emulsifying drug delivery system, which confirmed that lymphatic route was involved in the absorption of larotaxel loaded self-emulsifying drug delivery system. What is more, in vivo antitumor experiment proved that the antitumor activity of oral larotaxel loaded self-emulsifying drug delivery system was significantly superior to oral larotaxel-Sol, which was close to intravenous larotaxel-Sol. In conclusion, self-emulsifying drug delivery system is a promising vehicle for the oral delivery of larotaxel.