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

1. General Introductionmucosa, and then dissemination follows. In contrast to the immuno-compromised host, inwhich MAC disease is usually limited to the lungs, in patients with AIDS, bacteremia is byfar the most common syndrome. Before the 1980s, infections with these bacteria wereuncommon in humans and were recognized as a slowly progressing pneumonitis in elderlypatients with chronic pulmonary disorders, particularly in patients with silicosis (18) and,occasionally, immunocompromised leukemic patients (19). Since 1981, however, numerousmedical institutions began to report cases of MAC bacteremia in AIDS patients (20) whichwere responsible for significant morbidity and mortality in human immunodeficiency virus(HIV)-positive patients (21). Disseminated infections with MAC organisms are diagnosed inonly 3% of HIV-positive patients at the time of AIDS diagnosis (22). However, theseinfections are found in about half of the autopsied patients with AIDS (23). MAC isolates areintracellular pathogens resistant to many of the standard antituberculosis drugs. In many casesthis resistance is due to the low levels of drug permeation into macrophages, as manyantibiotics are unable to traverse the cell membranes, making it difficult to achieve sufficientconcentrations at the infection sites (24, 25).Nevertheless, it was not until the post-human immunodeficency virus (HIV) era, that renewedinterest became widespread in mycobacterial diseases in the immunocompromised host.Several reasons for such interest are the following. First, re-emergence of TB in countrieswhere this type of disease was in the way of eradication, was puzzling. Second, MOTT thatwere generally quite rarely isolated before the advent of AIDS, but represented before therecently used efficient antiretroviral therapies, have a considerable role in morbidity andmortality. This was particularly true for the M. avium complex (MAC) because theseorganisms are the single most important cause of disseminated bacterial infection in AIDSpatients (26). Third the number of cases of infection with multiply-drug-resistant (MDR) ofMT and MAC is increasing and this has compromised both treatment and control programmesworldwide. The rising prevalence of MDR strains has resulted in outbreaks and individualcases that are a problem to treat and are often fatal. Worldwide, TB and disseminated MACdisease, both contribute substantially to morbidity and mortality in this population.Among the mycobacterial genus, the vast majority of species are saprophytic belonging to theenvironmental microflora. They are present at different latitudes, and could be isolated fromsoil, and water. Mycobacteria are aerobic, Gram-positive, non-motile bacilli with a highmycolic acid content in their cell wall that enables intracellular survival within mononuclearphagocytes.12