Background: 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.
Objective: 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).
Method: 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.
Result: 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
Conclusion: 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.