Lactose-Conjugated PLGA Nanoparticles for Enhanced Delivery of Rifampicin to the Lung for Effective Treatment of Pulmonary Tuberculosis.

Lactose conjugated poly(lactic co-glycolic acid) nanoparticles (L-PLGA-NPs) were investigated for lung delivery of rifampicin for effective treatment of pulmonary tuberculosis. Lactose-PLGA conjugate was synthesized using lactose and PLGA and characterized by infrared spectroscopy. L-PLGA-NPs were prepared by the solvent displacement method. NPs were characterized for shape, particle size, zeta potential, and percent drug entrapment. The size of NPs was found to be in the range 121-184 nm and maximum drug payload was found to be 38.4-42.2%. Average size and drug payload was found to be greater in the case of L-PLGA-NPs as compared to unconjugated NPs. The results of the in vitro release profile, which was determined using the dialysis technique, demonstrated that noncoupled NPs release a comparatively higher percent of drug than lactose coupled NPs. Fluorescence studies revealed the enhanced uptake of L-PLGA-NPs in the lung tissue when compared with unmodified PLGA NPs. Intravenous administration of free drug solution resulted in a high concentration of drug in serum while it was much less in the case of PLGA NPs. Coupling of the NPs with lactose significantly enhanced the lung uptake of drug, which is reflected in the recovery of a higher percentage of dose from the lungs as compared to that recovered in the case of uncoupled drug-loaded NPs and plain drug solution.