chitosan and plga microspheres as drug delivery ... - UniCA Eprints

1. General Introductionobserved that particles reaching the lungs are phagocytosed rapidly by alveolar macrophages.Although phagocytosis and sequestration of inhaled powders may be a problem for drugdelivery to other cells comprising lung tissue, it is an advantage for chemotherapy of TB.Phagocytosed microparticles potentially can deliver larger amounts of drug to the cytosol thanoral doses. Moreover, microparticles have the potential for lowering dose frequency andmagnitude, which is especially advantageous for maintaining drug concentrations andimproving patient compliance. It may therefore be advantageous to incorporate inhalablemicroparticles containing multiple drugs in a inhalation system for chemotherapy of TB.Because of its biodegradability and biocompatibility, poly (lactide-co-glycolide) (PLGA; asynthetic polymer) has been a popular choice as a drug carrier. Patrick O’Hara et all. byemploying solvent evaporation as well as spray drying methods, PLGA microparticlesencapsulating rifampicin were prepared (179). The microspheres were administered viainsufflation or nebulization to guinea pigs, 24 h before aerosol infection with M. tuberculosisH37Rv. The model was adopted as a post-treatment screening method for antimicrobialefficacy. The assessment of colony forming units (cfu) 28 days post-infection showed a dose–effect relationship, i.e. lower cfu with higher doses of microspheres. The cfu count wassignificantly reduced compared with free rifampicin. With a similar experimental approach,the authors next evaluated the effect of repeated dosing of the microspheres. At 10 days postinfection,half of the treatment group received a second dose of the microspheres. There was asignificant reduction in cfu in lungs (but not in spleens) in the case of animals receiving asingle dose of the formulation, whereas two doses resulted in a significant decrease in cfu inlungs as well as in spleens. It was realized that besides the methodology involved inmicroparticle preparation, the surface characteristics of dry powders also play a key role inpredicting particle dispersion and pulmonary deposition. Although the results with rifampicinloadedmicrospheres proved to be encouraging, it was necessary to incorporate other ATDsbecause the disease requires multidrug therapy for its cure. Hence, other investigatorsencapsulated isoniazid with rifampicin in polylactide microparticles for dry powder inhalationto rats. Drug concentrations inside the alveolar macrophages were found to be higher than thatresulting from systemic delivery of free drugs, an indication of the rapid phagocytic uptakeand cytosolic localization of the drug-loaded microparticles. The authors discussed that sincealveolar macrophages migrate to secondary lymphoid organs, loading these cells withmicroparticles might lead to transport of drugs to those sites where macrophages migrate(mimicking the course of spread of mycobacteria).33