Thermosensitive poly-(d, l-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(d, l-lactide-co-glycolide) hydrogels for multi-drug delivery. (August 2014)

• Record Type: Journal Article
• Authors: Cho, Hyunah; Kwon, Glen S.
• Is Part Of: Journal of drug targeting. Volume 22:Number 7(2014)
• Page Start: 669
• Page End: 677
• Publication Date: 2014-08
• Subjects: Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.3109/1061186X.2014.931406
• Languages: English
• ISSNs: 1061-186X

Abstract

<abstract> <title>Abstract</title> <p>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-(<sc>d, l</sc>-lactide-co-glycolide)-<italic>block</italic>-poly(ethylene glycol)-<italic>block</italic>-poly-(<sc>d, l</sc>-lactide-co-glycolide) (PLGA-<italic>b</italic>-PEG-<italic>b</italic>-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-<italic>b</italic>-PEG-<italic>b</italic>-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)-<italic>block</italic>-poly(<sc>d, l</sc>-lactic acid) (PEG-<italic>b</italic>-PLA) micelles in solution <italic>via</italic> 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.</p> </abstract>