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

1. General Introductionis the fact that the etiological agent, MTB, has the ability to persist intracellularly in the hostmacrophage for long periods of time. This becomes even more important when one considersthe ability of MTB to persist in a dormant state, thus giving rise to a large group of infectedindividuals who carry the organism in a subclinical state without having active disease.The term MAC was coined after debate as to whether Mycobacterium intracellularerepresented a distinct species or was merely a variant of M avium (39, 40, 41). Traditionally,the MAC has been divided into serotypes using agglutination reactions, immunodiffusion,skin testing with sensitins, biochemical reactions on culture, or a combination of these (41).Molecular techniques have more recently been used to clarify the MAC group (42, 43). M.avium and related species are ubiquitous, saprophytic organisms commonly found in surfacewaters such as salt or fresh-water marshes, ponds, lakes, or soil. Animals, including people,are commonly exposed to these organisms (41). M. avium may give rise to disease ifintroduced in sufficient numbers through a breach in the skin or via alveolar deposition. Inimmune competent hosts, such events would cause localised infections, although generaliseddisease may arise in patients with compromised cell-mediated immunity (13).Even though the availability of powerful anti-tubercular drugs (ATD) such as rifampicin(RFP), isoniazid (INH) and pyrazinamide (PZA) makes TB and MOTT infections, curablediseases, the latter is far from eradication, the main reason being that multiple anti-tunerculardugs (ATD) need to be administered for 6-9 months. Patients often find it troublesome tobegin their day with a mouthful of pills. Further, as clinical symptoms improve, they may notconsider the need to continue ATD and may actually forget to take the drugs. All these factorsresult in non-compliance and eventually lead to therapeutic failure.1.2. Alveolar Macrophages and MTB/MACMTB and MAC are facultative intracellular micro-organisms that can survive and multiplyintra-cellularly and are protected from host defence mechanism. They interact mainly withmacrophages in the alveolar space of the lung, where they are able to invade and replicate inboth cell types. Their intracellular location serves as reservoir which is thought to be ofimportance in recurrent infections.Macrophages are present in all major compartment of the body and they are particularlyinvolved in removing foreign particles and micro-organism from the blood. After beingremoved from the blood, the behaviour of the micro-organism in the macrophage becomes ofgreat importance. Killing of the micro-organism could mean termination of the infection,14