Tuberculosis (TB) continues to be a major infectious burden worldwide. Even though the
availability of powerful antitubercular
drugs (ATD) such as rifampicin (RIF), isoniazid (INH)
and pyrazinamide (PZA) makes TB a curable disease, the latter is far from eradication, the
main reason being that multiple ATD need to be administered for 6-9 months.
If the currently available ATD could be modified in such a way so as to release the
drugs in a slow and sustained manner, it would be possible to reduce the dosing frequency
thereby improving compliance. Liposomes have long been known to serve as
drug carriers. They are composed of a lipid shell surrounding an aqueous core containing the
drug of interest. These liposomes were modified so as to reduce their non-specific uptake by the reticuloendothelial system and to make them lungspecific.The preparations were stable, nontoxic
and a single intravenous (i.v.)
administration produced therapeutic plasma/tissue drug levels for 5 – 7 days. Keeping in mind that pulmonary TB is the commonest form of TB and alveolar macrophages are the abode of M.tuberculosis, the administration of ATD via the respiratory route is an exciting possibility. Besides liposomes,work has been carried out with subcutaneous (s.c.) polymeric
microparticle based ATD delivery systems. PLG is biocompatible, biodegradable4and a single s.c. injection not only maintained therapeutic drug levels for 6–7 weeks but also demonstrated significant chemotherapeutic efficacy in murine TB model.Moreover, with a
few modifications in the preparation methodology, we succeeded in reducing the particle size (i.e., PLG microparticles to PLG nanoparticles). The nanoparticles were remarkably advantageous in terms of a high drug encapsulation efficiency, low polymer consumption, better sustained release profile,higher oral bioavailability and last but not the least, complete bacterial clearance in infected
mice following just five shots orally every 10 days.