PMID- 29031952
OWN - NLM
STAT- MEDLINE
DCOM- 20180911
LR  - 20220331
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 107
IP  - 2
DP  - 2018 Feb
TI  - Antitumor Efficacy and Toxicity of 5-Fluorouracil-Loaded 
      Poly(Lactide Co-glycolide) Pellets.
PG  - 690-697
LID - S0022-3549(17)30694-9 [pii]
LID - 10.1016/j.xphs.2017.10.005 [doi]
AB  - 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.
CI  - Copyright (c) 2018 American Pharmacists Association(R). Published by Elsevier Inc. 
      All rights reserved.
FAU - Leelakanok, Nattawut
AU  - Leelakanok N
AD  - Division of Pharmaceutics and Translational Therapeutics, University of Iowa 
      College of Pharmacy, Iowa City, Iowa 52242.
FAU - Geary, Sean M
AU  - Geary SM
AD  - Division of Pharmaceutics and Translational Therapeutics, University of Iowa 
      College of Pharmacy, Iowa City, Iowa 52242.
FAU - Salem, Aliasger K
AU  - Salem AK
AD  - Division of Pharmaceutics and Translational Therapeutics, University of Iowa 
      College of Pharmacy, Iowa City, Iowa 52242. Electronic address: 
      aliasger-salem@uiowa.edu.
LA  - eng
GR  - P30 CA086862/CA/NCI NIH HHS/United States
GR  - P30 ES005605/ES/NIEHS NIH HHS/United States
GR  - P50 CA097274/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20171012
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Carriers)
RN  - 0 (Drug Implants)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*adverse effects/chemistry/*pharmacology
MH  - Colonic Neoplasms/drug therapy
MH  - Delayed-Action Preparations/adverse effects/chemistry/pharmacology
MH  - Drug Carriers/chemistry
MH  - Drug Delivery Systems/methods
MH  - Drug Implants/*adverse effects/chemistry/*pharmacology
MH  - Female
MH  - Fluorouracil/*adverse effects/chemistry/*pharmacology
MH  - Lactic Acid/*chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Particle Size
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Thymoma/drug therapy
PMC - PMC5768445
MID - NIHMS912625
OTO - NOTNLM
OT  - 5-FU
OT  - 5-fluorouracil
OT  - Poly(lactic/glycolic) acid (PLGA, PLA)
OT  - colon cancer
OT  - controlled/sustained release/delivery
OT  - thymoma cancer
COIS- Conflicts of interest Authors declare no conflicts of interest.
EDAT- 2017/10/17 06:00
MHDA- 2018/09/12 06:00
PMCR- 2019/02/01
CRDT- 2017/10/17 06:00
PHST- 2017/07/15 00:00 [received]
PHST- 2017/10/03 00:00 [revised]
PHST- 2017/10/04 00:00 [accepted]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2018/09/12 06:00 [medline]
PHST- 2017/10/17 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - S0022-3549(17)30694-9 [pii]
AID - 10.1016/j.xphs.2017.10.005 [doi]
PST - ppublish
SO  - J Pharm Sci. 2018 Feb;107(2):690-697. doi: 10.1016/j.xphs.2017.10.005. Epub 2017 
      Oct 12.