Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation

Kaili Hu,¹ Shan Cao,^1,2 Fuqiang Hu,³ Jianfang Feng<sup>1

1</sup>Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ²Pharmacy Department, Baoshan Central Hospital, Shanghai, ³School of Pharmacy, Zhejiang University, Hangzhou, China

Abstract: The aim of this research work was to investigate the potential of lecithin nanoparticles (LNs) in improving the oral bioavailability of docetaxel. Docetaxel-loaded LNs (DTX-LNs) were prepared from oil-in-water emulsions and characterized in terms of morphology, size, zeta potential, and encapsulation efficiency. The in vitro release of docetaxel from the nanoparticles was studied by using dialysis bag method. Caco-2 cell monolayer was used for the in vitro permeation study of DTX-LNs. Bioavailability studies were conducted in rats and different pharmacokinetic parameters were evaluated after oral administration of DTX-LNs. The results showed that DTX-LNs had a mean diameter of 360 ± 8 nm and exhibited spherical shape with smooth surface under transmission electron microscopy. The DTX-LNs showed a sustained-release profile, with about 80% of docetaxel released within 72 hours. The apical to basolateral transport of docetaxel across the Caco-2 cell monolayer from the DTX-LNs was 2.14 times compared to that of the docetaxel solution (0.15 × 10^-5 ± 0.016 × 10^-5 cm/second versus 0.07 × 10^-5 ± 0.003 × 10^-5 cm/second). The oral bioavailability of the DTX-LNs was 3.65 times that of docetaxel solution (8.75% versus 2.40%). These results indicate that DTX-LNs were valuable as an oral drug delivery system to enhance the absorption of docetaxel.

Keywords: lecithin nanoparticles, oral delivery, docetaxel, bioavailability