Chitosan microspheres as an alveolar macrophage delivery system of ofloxacin via pulmonary inhalation

Abstract

Because Mycobacterium tuberculosis, which causes tuberculosis, survives mainly in the alveolar macrophages, the remedial efficiency of anti-tuberculosis drugs such as ofloxacin may be improved by their direct delivery to the lungs via pulmonary inhalation. For this purpose, ofloxacin-loaded, glutaraldehyde-crosslinked chitosan microspheres (OCMs) were prepared using a water-in-oil emulsification method. The particle size of the OCMs was around 1-6 mu m, and the content of ofloxacin was 27% (w/w). A twin-stage impinger (TSI) study revealed that the device-removal efficiency of the drug from the capsule and the arrival rate of the drug to stage II of the apparatus were substantially improved for OCMs compared to ofloxacin itself (i.e., 81 vs. 98% and 13 vs. 45%, respectively). Also, the in vitro uptake of ofloxacin from the OCMs to alveolar macrophages (NR8383) was substantially accelerated: the cellular ofloxacin concentrations at 4 and 24 h after the application were >3.5-fold greater than those for free ofloxacin. The above results indicate that pulmonary inhalation of OCMs might improve the delivery efficiency of ofloxacin to the alveolar macrophages, thereby shortening the length of time that is required to cure tuberculosis with the drug-usually at least 6 months when administered orally. (C) 2012 Elsevier B. V. All rights reserved.