title: Thermosensitive poly-(d,l-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(d,l-lactide-co-glycolide) hydrogels for multi-drug delivery.
abstract: A current treatment strategy for peritoneal ovarian cancer is a combination of peritoneal surgery and multi-drug-based chemotherapy that often involves intraperitoneal (IP) injection. A thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogel platform (thermogels) enabled gel loading of poorly work-soluble paclitaxel (cytotoxic agent), 17-allylamino-17-demethoxygeldanamycin (17-AAG, heat shock protein inhibitor), and rapamycin (mammalian target of rapamycin protein inhibitor). PLGA-b-PEG-b-PLGA thermogels (15%) carrying paclitaxel, 17-AAG, and rapamycin (named Triogel) made a successful transition from a free-flowing solution below ambient temperature to a gel depot at body temperature. Triogel gradually released paclitaxel, 17-AAG, and rapamycin at an equal release rate in response to the physical gel erosion. In an ES-2-luc ovarian cancer xenograft model, a single IP injection of Triogel (60, 60, and 30 mg/kg of paclitaxel, 17-AAG, and rapamycin, respectively) significantly reduced tumor burden and prolonged survival of ES-2-luc-bearing nude mice without notable systemic toxicity relative to those delivered by poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles in solution via IP or intravenous (IV) injection route. These results show a great potential of a biodegradable thermogel platform carrying multi-drugs for IP chemotherapy in peritoneal ovarian cancer.
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin , Madison, WI , USA.
authors: Hyunah
authors: H
authors: Cho
authors: Glen S
authors: GS
authors: Kwon
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D016227:Benzoquinones / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D065546:Drug Liberation; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D047029:Lactams, Macrocyclic / Q000008:administration & dosage*; D008819:Mice, Nude; D015394:Molecular Structure; D017239:Paclitaxel / Q000008:administration & dosage*; D044367:Phase Transition; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D020123:Sirolimus / Q000008:administration & dosage*; D044366:Transition Temperature; D023041:Xenograft Model Antitumor Assays
chemical_list: D016227:Benzoquinones; D004337:Drug Carriers; D004338:Drug Combinations; D020100:Hydrogels; D047029:Lactams, Macrocyclic; D011091:Polyesters; C000595637:poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; C112765:tanespimycin; D017239:Paclitaxel; D020123:Sirolimus
keywords: 17-AAG; PLGA-b-PEG-b-PLGA; multi-drug delivery; ovarian cancer; paclitaxel; raamycin; regel