Novel nanoparticles for Tuberculosis chemotherapy

Abstract

Current therapeutic management of tuberculosis is inadequate due to non-compliance, lengthy course of treatment and drug- related side effects. In order to address these setbacks, the authors are developing a nanotechnology drug delivery system whereby anti- TB drugs can be administered in a single dose that maintains an active level of the drug for at least a week. Poly (lactic-co-glycolic acid) (PLGA) was used to prepare a multiple nano-emulsion which was subsequently lyophilized via freeze drying or spray drying. The resulting nanoparticles were characterised based on size, zeta potential, morphology and drug encapsulation efficiency. Particle uptake was analyzed in CaCo-2 cells via confocal microscopy, as well as in vivo, by analyzing macrophages of peritoneum cells of mice. Nano-sized polymeric PLGA particles of size ranging from 200-300 nm (zeta potential ~16 mV) were synthesized, with a smooth spherical surface and a drug encapsulation efficiency of 50-65% for INH and RIF. It was observed from the in vitro release assays, that the drugs were released in a slow manner compared to free drugs. The particles were taken up in vitro by CaCo-2 cells as well as in vivo by macrophages of the peritoneum. The uptake of the particles by cells will enable improved bioavailability of the encapsulated drugs, in that intracellular drug release can be obtained. Due to the slow degradation, and thus slow release mechanism, of the carrier systems it is envisaged that using nano-based delivery systems can prolong drug release, thus minimising dose and dosage frequency of anti-TB drugs