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 (HAART), there has been a reduction in HIV viral titers and a concomitant decrease in AIDS-related Kaposi's sarcoma. However, as failure rates of HAART approach 30%, concerns arise regarding resurgence in AIDS-KS. Current AIDS-KS therapies fail to provide sustained remissions and yet also result in significant 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 from biodegradable, locally injectable, controlled-release poly(lactide-co-glycolide) (PLGA) microspheres. Local drug delivery systems such as PLGA microspheres can sustain therapeutic intralesional concentrations while minimizing deleterious systemic side effects, providing a pharmacologic advantage at the treatment site. Our data show that controlled release from PLGA microspheres augments doxorubicin cytotoxicity towards AIDS-KS cells without increasing toxicity in nonlesional cells from the AIDS-KS donors. Electron microscopic analysis revealed that PLGA microspheres possess a strong affinity for cell membranes, facilitating doxorubicin delivery to redox-sensitive cell membrane sites. Consistent with their speculated endothelial cell lineage, some of the AIDS-KS cells appeared to engulf microspheres via phagocytosis. Our results suggest that PLGA controlled-release doxorubicin microspheres have potential clinical applicability in management of AIDS-KS.
Mallery
S R
SR
College of Dentistry, Department of Oral and Maxillofacial Surgery and Pathology, Ohio State University, Columbus 43218-2357, USA.
Pei
P
P
Kang
J
J
Ness
G M
GM
Ortiz
R
R
Touhalisky
J E
JE
Schwendeman
S P
SP
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008297:Male; D008863:Microspheres; D011098:Polyglactin 910; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011098:Polyglactin 910; D004317:Doxorubicin