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Efficacy of microencapsulated rifampin in Mycobacterium tuberculosis-infected mice
D C Quenelle1, J K Staas, G A Winchester
1Infectious Disease Animal Models Group, Southern Research Institute, Birmingham, Alabama, USA.
Abstract:
Rifampin is a first-line drug useful in the treatment of tuberculosis. By using biocompatible polymeric excipients of lactide and glycolide copolymers, two microsphere formulations were developed for targeted and sustained delivery of rifampin, with minimal dosing. A small-microsphere formulation, with demonstrated ability to inhibit intracellularly replicating Mycobacterium tuberculosis H37Rv, was tested along with a large-microsphere formulation in an infected mouse model. Results revealed that by using a single treatment of the large-microsphere formulation, it was possible to achieve a significant reduction in M. tuberculosis H37Rv CFUs in the lungs of mice by 26 days postinfection. A combination of small (given as two injections on day 0 and day 7) and large (given as one injection at day 0) rifampin-loaded microsphere formulations resulted in significant reductions in CFUs in the lungs by 26 days, achieving a 1.23 log10 reduction in CFUs. By comparison, oral treatment with 5, 10, or 20 mg of rifampin/kg of body weight, administered every day, resulted in a reduction of 0.42, 1.7, or 1.8 log10 units, respectively. Thus the microsphere formulations, administered in one or two doses, were able to achieve results in mice similar to those obtained with a daily drug regimen within the range of the highest clinically tolerated dosage in humans. These results demonstrate that microsphere formulations of antimycobacterial drugs such as rifampin can be used for therapy of tuberculosis with minimal dosing.
Insights
New rifampin microsphere formulations offer targeted tuberculosis treatment. These sustained-release drug delivery systems achieve significant bacterial reductions with minimal dosing in mouse models.
Area of Science:
- Pharmacology
- Biomaterials Science
- Infectious Diseases
Background:
- Tuberculosis (TB) treatment relies on first-line drugs like rifampin.
- Developing effective drug delivery systems for sustained and targeted rifampin release is crucial for improving TB therapy.
- Minimizing dosing frequency can enhance patient compliance and treatment outcomes.
Purpose of the Study:
- To develop and evaluate novel rifampin-loaded microsphere formulations for targeted and sustained drug delivery.
- To assess the efficacy of these microsphere formulations in reducing Mycobacterium tuberculosis H37Rv bacterial load in an infected mouse model.
- To compare the therapeutic outcomes of microsphere formulations with conventional oral rifampin administration.
Main Methods:
- Two rifampin-loaded microsphere formulations (small and large) were prepared using biocompatible lactide and glycolide copolymers.
- The efficacy of small and large microsphere formulations was evaluated in a mouse model infected with Mycobacterium tuberculosis H37Rv.
- Bacterial colony-forming units (CFUs) in mouse lungs were quantified at 26 days postinfection to assess treatment effectiveness.
Main Results:
- A single dose of the large-microsphere formulation significantly reduced M. tuberculosis CFUs in mouse lungs by 26 days postinfection.
- A combination of small and large microsphere formulations (two and one dose, respectively) achieved a 1.23 log10 reduction in lung CFUs.
- These results were comparable to daily oral rifampin regimens at clinically relevant dosages, demonstrating the potential of microsphere formulations.
Conclusions:
- Rifampin-loaded microsphere formulations provide a promising strategy for targeted and sustained delivery of antimycobacterial drugs.
- These formulations can achieve significant reductions in tuberculosis bacterial load with minimal dosing, potentially improving treatment efficacy and patient adherence.
- Microsphere-based drug delivery systems represent a viable therapeutic approach for managing tuberculosis.