Controlled-release of doxorubicin from poly(lactide-co-glycolide) microspheres significantly enhances cytotoxicity against cultured AIDS-related Kaposi's sarcoma cells

Subsequent to the introduction of highly active antiretroviral therapy (HAA RT), there has been a reduction in HIV viral titers and a concomitant decre ase in AIDS-related Kaposi's sarcoma. However; as failure rates of HAART ap proach 30%, concerns arise regarding resurgence in AIDS-KS. Current AIDS-KS therapies fail to provide sustained I emissions and yet also result in sig nificant morbidity. Although partially effective, systemic chemotherapy is particularly debilitating to AIDS patients. In this report, we examined the co-incubation of AIDS-KS cells with doxorubicin which was slowly delivered fi om biodegradable, locally injectable, controlled-release poly(lactide-c o-glycolide) (PLGA) microspheres. Local drug delivery systems such as PLGA microspheres can sustain therapeutic intralesional concentrations while min imizing deleterious systemic side effects, providing a pharmacologic advant age at the treatment site. Our data show that controlled release fl-om PLGA microspheres augments doxorubicin cytotoxicity towards AIDS-KS cells witho ut increasing toxicity in nonlesional cells fi om the AIDS-KS donors. Elect ron microscopic analysis revealed that PLGA microspheres possess a strong a ffinity for cell membranes facilitating doxorubicin delivery to redox-sensi tive cell membrane sites. Consistent with their speculated endothelial cell lineage, some of the AIDS-KS cells appealed to engulf microspheres via pha gocytosis. Our results suggest that PLGA controlled-release doxorubicin mic rospheres have potential clinical applicability in management of AIDS-KS.