Raja Kalluru
Stanford University, USA
Posters & Accepted Abstracts: J Nanomed Nanotechnol
The global burden of tuberculosis (TB) and increasing incidence of drug resistance, and lengthy treatment courses pose a challenge to TB elimination goal set by the WHO. Development of novel drugs to target genes responsible for drug resistance in pathogens and to minimize the drug dose needed to treat infection using nanoparticle-based drug delivery approaches are vital to shortening the course of TB therapy. Biodegradable Nanoparticles (NPs) are increasingly used as vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (PLGA) and has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis. Our goal here was twofold: First goal is to test resolve the controversial issue of whether, after phagocytic uptake, PLGA NPs remain membrane-bound or whether they escape into the cytoplasm, as has been widely claimed and NPs that enclosed sufficient anti tb drug to efficiently clear macrophages of infection with Mycobacterium bovis BCG. Our data collectively argue that PLGA NPs remain membrane-enclosed in macrophages. Importantly, provided that the NPs are fabricated with sufficient antibiotic, one dose given after infection is sufficient to efficiently clear the BCG infection after 9–12 days of treatment, as shown by estimates of the number of bacterial colonies in vitro. Second goal was to compare conventional therapy vs Biodegradable nanoparticle-based therapies. Against mycobacteria in macrophage in model systems. Clearly our results indicate the nanoparticle therapy is minimizing the drug needed to clear the infection.