Pharmacokinetic Evaluation of Wheat Germ Agglutinin-Grafted Nanoparticles of Mometasone Furoate

摘要

The aim of the investigation was to assess the pharmacokinetic parameters of wheat germ agglutinin (WGA)-grafted nanoparticles of mometasone furoate (MF), after intratracheal instillation in rats. PLGA (50:50) nanoparticles (NPs) loaded with MF were prepared by emulsion-solvent evaporation technique. WGA was conjugated to spherical MF loaded nanoparticles by carbodiimide coupling yielding a ligand density of 10-15μg WGA / mg NP. The nanoparticles were characterized for size, zeta potential, entrapment efficiency and in-vitro drug release. Plain drug, MF nanoparticles and WGA-grafted MF nanoparticles were administered intratracheally in rats and at different time intervals drug levels in the lung tissue and bronchoalveolar lavage (BAL) were estimated using HPLC. Cumulative MF-release from unconjugated and conjugated MF-nanoparticles after 2 weeks was 68% and 55% of the initial drug loading. From the lung MF concentration vs time plot, AUC for WGA-MF-NPs and MF-NPs was found to be 5.9 and 3.8 times higher than AUC for plain MF. This improvement of intracellular drug uptake by means of WGA-conjugation might be due to bioadhesive nature of the lectin which provides an intimate contact to lung mucosal cells followed by facilitated transcytosis as confirmed by improved pharmacokinetic behaviour. All in all, these findings are expected to contribute for better management of asthma to overcome the limitation of short lived action associated with dry powder inhalers.