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Title: Antitumor Efficacy and Toxicity of 5-Fluorouracil-Loaded Poly(Lactide Co-glycolide) Pellets.

Authors: Leelakanok, Nattawut; Geary, Sean M; Salem, Aliasger K

Published In J Pharm Sci, (2018 Feb)

Abstract: The aim of this study was to formulate a biodegradable implant capable of imparting local antitumor activity through the sustained release of the chemotherapeutic agent, 5-fluorouracil (5-FU). Thus, injectable pellets (<1.2 mm diameter) made from poly(lactide co-glycolide) (PLGA) and loaded with 5-FU at varying drug:polymer ratios were fabricated using hot-melt extrusion and tested for their ability to provide sustained release of 5-FU in in vitro and in vivo settings. In addition, these formulations were compared against soluble 5-FU for their antitumor activity in vivo as well as for their toxicity. It was demonstrated that the release rate of 5-FU from PLGA pellets was directly related to the percentage of 5-FU in the pellets. PLGA pellets loaded with 50% w/w 5-FU exhibited comparable, and significantly enhanced, antitumor activity (as measured by tumor volumes and survival) in vivo in a thymoma and colon cancer model, respectively, when compared to an equivalent bolus dose (120 mg/kg) of soluble 5-FU. We concluded that 5-FU-loaded PLGA pellets were more effective and specifically less erythrotoxic than 5-FU bolus injections and therefore may prove to be of benefit as an intraoperative adjunct therapy for patients with cancers that are sensitive to 5-FU and who are undergoing tumor resection.

PubMed ID: 29031952 Exiting the NIEHS site

MeSH Terms: Animals; Antimetabolites, Antineoplastic/adverse effects*; Antimetabolites, Antineoplastic/chemistry; Antimetabolites, Antineoplastic/pharmacology*; Colonic Neoplasms/drug therapy; Delayed-Action Preparations/adverse effects; Delayed-Action Preparations/chemistry; Delayed-Action Preparations/pharmacology; Drug Carriers/chemistry; Drug Delivery Systems/methods; Drug Implants/adverse effects*; Drug Implants/chemistry; Drug Implants/pharmacology*; Female; Fluorouracil/adverse effects*; Fluorouracil/chemistry; Fluorouracil/pharmacology*; Lactic Acid/chemistry*; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Particle Size; Polyglycolic Acid/chemistry*; Polylactic Acid-Polyglycolic Acid Copolymer; Thymoma/drug therapy

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