Nanostructured lipid carriers as oral delivery systems for improving oral bioavailability of nintedanib by promoting intestinal absorption.

The aim of this study was to fabricate nanostructured lipid carriers, NLCs, of nintedanib (BIBF) to improve its oral bioavailability. Two types of NLCs loaded with BIBF (BIBF-NLCs-1 and BIBF-NLCs-2) were prepared by the melt-emulsification technique. BIBF-NLCs-1 and BIBF-NLCs-2 showed nanoscale particle sizes of 142.70 ± 0.85 nm and 7.99 ± 0.06 nm, and both were positive zeta potential. Study on Caco-2 cells showed that BIBF-NLCs-1 exhibited distinct advantages at the cytological level. The oral bioavailability of BIBF-NLCs-1 and BIBF-NLCs-2 was extremely improved 3.13-fold and 2.39-fold respectively compared with BIBF solution (BIBF-Sol). And in vivo anti-tumor efficiency study in mice bearing LLC lung tumor indicated that BIBF-NLCs-1 and BIBF-NLCs-2 had excellent tumor inhibition. Besides, the two NLCs did not increase the risk of liver damage and can even reduce the incidence of gastrointestinal irritation of BIBF to some extent. In summary, NLCs are a potential oral delivery system to improve the bioavailability of BIBF by promoting intestinal absorption.