No abstract

Mycobacterium tuberculosis (TB) is one of the leading causes of death and is intensified by HIV co-infection and multidrug resistance. Some of the problems associated with currently available drug treatment for TB are poor permeation and low bioavailability. Many drug delivery systems have indicated improvement in targeteddelivery of various drug molecules and among these, biodegradable and biocompatible polymers such as poly(D,L-lactide-co-glycolide) (PLGA) have been shown to enhance intracellular uptake of drug candidates when formulated as nanoparticles. PLGA nanoparticles were prepared by means of a double emulsion solvent evaporation technique and evaluated in terms of size, encapsulation efficiency, surface charge, isoniazid release and in vitro transport. The nanoparticles have an average size of 237 nm, and were previously shown to be distributed in several tissues after oral administration without triggering an immune response. This study focussed on the in vitro permeation of the PLGA nanoparticles across different membranes and showed that although the nanoparticles are efficiently delivered across the intestinal epithelium, they release encapsulated isoniazid very slowly after being transported. This may improve the treatment efficiency due to continuous release of the isoniazid after effective delivery of the nanoparticulate system across the intestinal epithelium, however, this should be confirmed by future in vivo studies.