Gelatin nanocarriers as potential vectors for effective management of tuberculosis

The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticulate delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through transmission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistribution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264+/-11.2 nm with low PDI suggesting the narrow particle size distribution. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis.