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

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.

Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation Formulations of Rifampicin and Rifabutin

“…(46) Thus, size is an important parameter for microparticles meant for targeting Mycobacterium tuberculosis within alveolar macrophages. Many authors have reported internalization of microparticles by alveolar macrophages (47)(48)(49) and their visualization by fluorescence microscopy or staining techniques. (50) FPF, fine particle fraction; GSD, geometric standard deviation; M, month; MMAD, mass median aerodynamic diameter; RT, room temperature; RH, relative humidity.…”

Selective delivery of rifampicin incorporated into poly(dl-lactic-co-glycolic) acid microspheres after phagocytotic uptake by alveolar macrophages, and the killing effect against intracellular Mycobacterium bovis Calmette–Guérin

“…The microspheres can be taken up into the infected macrophages by phagocytosis. In recent studies on drug delivery against M. tuberculosis infection, microspheres composed of liposomes or biodegradable polymers such as poly(DL-lactide-co-glycolide) (PLGA) have been used [3]. In these studies, the drugs contained in these carriers showed higher transfer rates and longer half-lifes than free drugs in the organs such as lung [4], liver [5,6], and spleen [7].…”

The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

“…This method of delivery has certain advantages, including (1) the frequency of medication can be reduced due to a sustainedrelease formulation [20]; (2) the dose can be reduced compared to oral administration by delivering drugs specifically to AMs [21][22][23][24][25][26];…”