Mannosylated gelatin nanoparticles of licorice for use in tuberculosis: Formulation, in vitro evaluation, in vitro cell uptake, in vivo pharmacokinetics and in vivo anti-tubercular efficacy

Abstract

Tuberculosis is a leading cause of mortality and morbidity worldwide and there is an urgent need to develop new efficacious medicines for its treatment. In this study, gelatin nanoparticles containing anti-tubercular licorice extract were prepared by double desolvation technique and conjugated with mannose for active targeting to macrophages. Nanoparticles were characterized for particle size, surface charge, drug entrapment, particle shape by transmission electron microscopy, in vitro drug release and in vitro uptake in RAW 264.7 cells. The optimized formulations showed a particle size of around 300 nm, surface charge of −21.6 mV and drug entrapment of 24%. As compared to extract, the formulation exhibited significantly improved in vitro dissolution. Mannosylation did not significantly alter the drug release profile. In vitro studies showed enhanced cell uptake of mannosylated formulation. In vivo pharmacokinetics showed that the mannosylated nanoparticles maintained therapeutically relevant drug levels in the body for 24 h. In vivo anti-tubercular efficacy of the mannosylated nanoparticles in murine tuberculosis model showed statistically significant reduction in bacterial counts in lungs and spleen of Mycobacterium tuberculosis H37Rv infected mice as compared to untreated animals. The optimized mannosylated nanoparticles show promise and have the potential to be developed as effective anti-tubercular agent.