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<p>Tuberculosis (TB), particularly its multi-drug-resistant (MDR-TB) forms, remains a significant global health challenge. This study focused on developing and evaluating Mesoporous Silica Nanoparticles (MSNPs) as a delivery platform for D-Cycloserine (DCS) and Moxifloxacin (MXF) to enhance treatment efficacy. Specifically, this research investigated MSNP co-encapsulation (DCS-MXF@MSNPs). The dual-drug formulation was optimized using Central Composite Design (CCD), achieving an entrapment efficiency (%EE) of 77.0% while maintaining a high surface area (800 m<sup>2</sup>/g), confirming that drug loading occurred without pore blockage. Characterization showed a particle size of 128.0&#xa0;nm and a zeta potential of -23.5&#xa0;mV. In vitro release studies demonstrated pH-responsive kinetics: at pH 7.4, release followed Fickian diffusion (n = 0.48), whereas at pH 5.5 (simulating the macrophage environment), release accelerated to 75% at 24&#xa0;h via a shift toward anomalous transport (n = 0.58). In vivo pharmacokinetic studies in Wistar rats confirmed significantly enhanced drug exposure, with a composite AUC<sub>0-∞</sub> of 50.0 ± 4.2&#xa0;µg/ml.h (both DCS and MXF from the co-loaded DCS-MXF@MSNPs (F4), and a prolonged mean residence time (MRT) of 18&#xa0;h. This system is ideal for the initial bactericidal phase of MDR-TB regimens, optimizing macrophage targeting where <i>M. tuberculosis</i> resides.</p> Graphical Abstract <p></p>

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Controlled Co-release of D-Cycloserine and Moxifloxacin from Mesoporous Nanoparticles for Synergistic MDR-TB Treatment

  • 期刊论文

  • 发表日期：

    2026年5月19日

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  • B. Naga Shubha,
  • Lalit Kumar,
  • V. N. Azger Dusthackeer,
  • Y. Padmanabha Reddy

摘要

Tuberculosis (TB), particularly its multi-drug-resistant (MDR-TB) forms, remains a significant global health challenge. This study focused on developing and evaluating Mesoporous Silica Nanoparticles (MSNPs) as a delivery platform for D-Cycloserine (DCS) and Moxifloxacin (MXF) to enhance treatment efficacy. Specifically, this research investigated MSNP co-encapsulation (DCS-MXF@MSNPs). The dual-drug formulation was optimized using Central Composite Design (CCD), achieving an entrapment efficiency (%EE) of 77.0% while maintaining a high surface area (800 m2/g), confirming that drug loading occurred without pore blockage. Characterization showed a particle size of 128.0 nm and a zeta potential of -23.5 mV. In vitro release studies demonstrated pH-responsive kinetics: at pH 7.4, release followed Fickian diffusion (n = 0.48), whereas at pH 5.5 (simulating the macrophage environment), release accelerated to 75% at 24 h via a shift toward anomalous transport (n = 0.58). In vivo pharmacokinetic studies in Wistar rats confirmed significantly enhanced drug exposure, with a composite AUC0-∞ of 50.0 ± 4.2 µg/ml.h (both DCS and MXF from the co-loaded DCS-MXF@MSNPs (F4), and a prolonged mean residence time (MRT) of 18 h. This system is ideal for the initial bactericidal phase of MDR-TB regimens, optimizing macrophage targeting where M. tuberculosis resides.

Graphical Abstract