Conjugate Delivery of D-Cycloserine and Moxifloxacin via Hydrolysable Cross Linkers -Mesoporous Silica Nanoparticles for Synergistic Effect on Multiple Drug Resistant on Tuberculosis

Background

The rise of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to global health. This study aimed to develop a novel drug delivery system using mesoporous silica nanoparticles (MSNPs) loaded with dual drug conjugates to combat MDR-TB.

Objective

To design, optimize, and evaluate MSNPs loaded with dual drug conjugates for enhanced treatment of MDR-TB.

Methods

Two dual drug conjugates, D-Cycloserine-Chloroacetyl chloride-Moxifloxacin (DCM) and D-Cycloserine-Succinyl chloride-Moxifloxacin (DSM), were synthesized via nucleophilic substitution reactions. The conjugates were evaluated for hydrolysability and loaded into MSNPs, which were optimized using Design Expert software. The MSNPs were characterized using FTIR, NMR, particle size analysis, zeta potential measurements, and SEM. In vitro drug release, in vivo pharmacokinetic studies, and in vitro microbiological investigations against M. tuberculosis H37Rv were conducted.

Results

The optimized MSNPs exhibited desirable characteristics, including a uniform mesoporous structure, high drug loading, controlled release, and enhanced bioavailability. DSM-loaded MSNPs demonstrated superior synergistic inhibitory activity against M. tuberculosis H37Rv compared to DCM and the free drug mixture.

Conclusion

This study highlights the potential of MSNPs loaded with dual drug conjugates, particularly DSM, as an effective strategy for MDR-TB treatment. This approach offers enhanced drug delivery, synergistic activity, and improved bioavailability, potentially overcoming challenges associated with MDR-TB.