Development and Optimization of Dual Drugs (Isoniazid and Moxiflox-acin) Loaded Functional PLGA Nanoparticles for the Synergistic Treatment of Tuberculosis.

The management of TB is difficult due to the resistance developed by Mycobacterium tuberculosis against anti-tubercular drugs causes the new challenges for treating and managing the disease. The objective of the study was to combat multiple drug resistance (MDR) exhibited by mycobacterium species by synthesizing Dual Drug Conjugate nanoparticle (DDC) using Isoniazid (INH) and Moxifloxacin (MOXI). The reaction was nucleophilic substitution using hydrolysable linkers like Chloroacetyl chloride (CAC) & Succinyl chloride (SCL). The drugs were covalently linked as INH-CAC-MOXI (DDC-1) and INH-SCL-MOXI (DDC-2). The DDC-1 & DDC-2 were subjected to hydrolysability tests at different pH solutions. The modified drugs were formulated into Poly (D, L-Lactic-co-Glycolide) nanoparticles using single emulsion technique. Design Expert® (version 8.0.1) software was used for designing, and evaluating the prepared formulation by employing response surface, optimal design of experiment technique. The prepared nanoparticles were characterized for compatibility studies using Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, particle size, size distribution, Zeta potential, drug entrapment efficiency and Scanning Electron Microscopy. Microbiological studies on pure drug and the conjugate indicated better activity of conjugate compared to pure drug alone or 1:1 physical mixture of drug. The nanoparticles were further subjected to drug release studies and accelerated stability studies. The present study offers a key to the challenge of loading different types of drugs onto the same drug delivery vehicle with efficient loading capacity, thus enabling better treatment for TB.