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Use of microsphere technology for targeted delivery of rifampin to Mycobacterium tuberculosis-infected macrophages
E L Barrow1, G A Winchester, J K Staas
1Mycobacteriology Research Unit, Southern Research Institute, Birmingham, Alabama 35205, USA. barrow@sri.org
Abstract:
Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages.
Insights
Rifampin-loaded microspheres effectively target host macrophages for sustained drug delivery. This formulation significantly reduced intracellular Mycobacterium tuberculosis growth compared to free rifampin.
Area of Science:
- Pharmacology
- Biotechnology
- Infectious Diseases
Background:
- Targeted drug delivery aims to improve therapeutic efficacy and reduce side effects.
- Macrophages are key host cells for intracellular pathogens like Mycobacterium tuberculosis.
- Rifampin is a crucial antibiotic for tuberculosis treatment, but intracellular efficacy can be limited.
Purpose of the Study:
- To develop and evaluate rifampin-loaded microspheres for targeted delivery to host macrophages.
- To assess the in vitro release kinetics and bioactivity of rifampin from microspheres.
- To determine the efficacy of microsphere-delivered rifampin against intracellular Mycobacterium tuberculosis.
Main Methods:
- Microspheres formulated using lactide-glycolide copolymers encapsulating rifampin.
- In vitro release studies and bioassays performed in murine J774 and human Mono Mac 6 cell lines.
- Treatment of Mycobacterium tuberculosis-infected cell lines with rifampin-loaded microspheres and assessment of colony-forming units (CFU).
Main Results:
- Bioactive rifampin was released from microspheres over a 7-day period in cell culture.
- Rifampin-loaded microspheres significantly reduced intracellular Mycobacterium tuberculosis CFU in infected monocytes.
- Microsphere-delivered rifampin demonstrated superior efficacy in controlling intracellular bacterial growth compared to free rifampin, despite low release percentage.
Conclusions:
- Rifampin-loaded microspheres provide effective sustained and targeted delivery to host macrophages.
- This formulation enhances the anti-mycobacterial activity against intracellular Mycobacterium tuberculosis.
- Microsphere technology offers a promising strategy for improving tuberculosis treatment.