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Antimicrobial Agents and Chemotherapy, October 1998, p. 2682-2689, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages

Esther L. W. Barrow,1 Gary A. Winchester,2 Jay K. Staas,2 Debra C. Quenelle,3 and William W. Barrow1,*

Mycobacteriology Research Unit,1 Drug Delivery Group,2 and Infectious Disease Animal Models Group,3 Southern Research Institute, Birmingham, Alabama 35205

Received 20 February 1998/Returned for modification 9 July 1998/Accepted 7 August 1998

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.

* Corresponding author. Mailing address: Mycobacteriology Research Unit, Southern Research Institute, 2000 Ninth Ave. South, Birmingham, AL 35205. Phone: (205) 581-2139. Fax: (205) 581-2877. E-mail: barrow{at}sri.org.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2682-2689, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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