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

Nattawut Leelakanok; Sean M Geary; Aliasger K Salem

doi:10.1016/j.xphs.2017.10.005

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

Journal article

Peer reviewed

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

Nattawut Leelakanok, Sean M Geary and Aliasger K Salem

Journal of pharmaceutical sciences, Vol.107(2), pp.690-697

02/2018

DOI: 10.1016/j.xphs.2017.10.005

PMID: 29031952

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https://www.ncbi.nlm.nih.gov/pmc/articles/5768445View

Open Access

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.

5-fluorouracil

Poly(lactic/glycolic) acid (PLGA, PLA)

thymoma cancer

controlled/sustained release/delivery

colon cancer

5-FU

Details

Title: Subtitle: Antitumor Efficacy and Toxicity of 5-Fluorouracil-Loaded Poly(Lactide Co-glycolide) Pellets
Creators: Nattawut Leelakanok
Sean M Geary
Aliasger K Salem
Resource Type: Journal article
Publication Details: Journal of pharmaceutical sciences, Vol.107(2), pp.690-697
DOI: 10.1016/j.xphs.2017.10.005
PMID: 29031952
NLM abbreviation: J Pharm Sci
ISSN: 0022-3549
eISSN: 1520-6017
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute, award: 5P30CA086862
Language: English
Date published: 02/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9983985716502771

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