Improved oral bioavailability of docetaxel by nanostructured lipid carriers: in vitro characteristics, in vivo evaluation and intestinal transport studies

Abstract

The objective of the current study was to explore the potential of nanostructured lipid carriers (NLC) for oral delivery of docetaxel (DTX) and investigate the absorption mechanism in vivo. Docetaxel-loaded nanostructured lipid carriers (DNLCs) were prepared by emulsification–ultrasonication and their physicochemical properties were characterized. Differential scanning calorimetry (DSC) demonstrated that the drug was present in a amorphous state and FTIR analysis suggested that the interaction of DTX and lipids involved hydrogen bonding and hydrophobic interactions. DNLCs were found to be stable in simulated gastrointestinal fluids and in vitro drug release studies revealed that the formulation exhibited sustained drug release for 48 h by Fickian diffusion. The drug absorption in the intestine was markedly improved by NLCs. An in vivo pharmacokinetic study demonstrated that the AUC_{0–24 h} for DNLCs (536.18 ± 91.21 ng mL⁻¹ h) was increased 4.31-fold compared with that of docetaxel solution (DTX-Sol). DNLCs could be absorbed into the enterocytes through both endocytosis and passive transport. The oral bioavailability of DNLCs was significantly reduced after the lymphatic transport pathway was blocked. The overall results showed that the NLCs were a very effective method for increasing the oral absorption of docetaxel.