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

1. General Introduction1.1. Pulmonary Mycobacterial Infections and Immuno-Compromised HostsPulmonary infections, due to a variety of pathogens, are important causes of morbidity andmortality today especially in immuno-compromised individuals.The main consequence of HIV infection is a progressive depletion and disfunction of T cells,with defects in macrophage and monocyte functions that have a central role in antimycobacterialdefences. Susceptibility to opportunistic pathogens has also been found inpatients with congenital T cell defects and in people treated with chemotherapeutic agents orirradiation that cause T cell depletion. Most prominent among these infections is pneumoniadue to Pneumocystis Carinii but there has also been a high incidence of mycobacterialinfections (1,2).Mycobacterial infection has been documented as a common opportunistic disease in patientswith acquired immunodeficiency syndrome (AIDS). At Memorial Sloan-Kettering CancerCenter more than 400 patients with AIDS have been followed. There have been 90documented cases of disseminated Mycobacterium Avium Complex (MAC) infection, 11cases of disease due to Mycobacterium Tuberculosis (MTB), and one case of combinedMAC-MTB infections (3).Tuberculosis (TB) has become a significant opportunistic disease among populations with ahigh incidence of AIDS. TB is most often due to Mycobacterium tuberculosis (MTB), and thelungs are the primary site of infection for the systemic pathogen but MTB can also affectcentral nervous system (meningitis), lymphatic system, circulatory system (Miliarytuberculosis), genitourinary system, bones and joints, (4). Among the various forms oftuberculosis, pulmonary tuberculosis is most commonly characterized by the involvement ofalveolar macrophages harboring a large number of tubercle bacilli. The bacilli secretemolecules that prevent phagosome–lysosome fusion. Moreover, due to their very hydrophobicwaxy cell wall, bacilli are resistant to digestion by lysosomal enzymes and hence resist thekilling effects of macrophages. Inside the macrophages the bacteria will be either destroyed orbegin replicating, or remain latent indefinitely. If replication is not prevented, the bacillimultiply and may eventually cause the macrophage to break. Problems created by bacterialinfection are linked to their ability to survive and multiply inside the body, especially in thelungs, and to the natural immune response of the infected host.10