PMID- 30040972
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20220408
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 550
IP  - 1-2
DP  - 2018 Oct 25
TI  - Effective sustained release of 5-FU-loaded PLGA implant for improving therapeutic 
      index of 5-FU in colon tumor.
PG  - 380-387
LID - S0378-5173(18)30522-2 [pii]
LID - 10.1016/j.ijpharm.2018.07.045 [doi]
AB  - In this study, a biodegradable implant composed of poly(lactide co-glycolide) 
      (PLGA) and 5-fluorouracil (5-FU) was fabricated by mold method and used to impede 
      the colon cancer via the local sustained release of 5-FU after transplanting into 
      the peritoneal cavity. To optimize the 5-FU-implant, different factors such type 
      of polymer, polymer-drug ratio, hydrophilic additives and organic solvents were 
      investigated based on in vitro 5-FU release behavior. The optimized 5-FU-implant 
      was subjected to evaluate the capacity of sustained release of 5-FU in vitro and 
      in vivo. In addition, the pharmacokinetics and bio-distribution of 5-FU-implant 
      were also tested in vivo after grafting into the peritoneal cavity in rat. 
      Moreover, different doses of 5-FU-implants were compared against 5-FU injection 
      for their antitumor activity in colon cancer model in nude mice and for their 
      safety in health rat. The results revealed that the optimized 5-FU-implant 
      possessed excellent sustained release of 5-FU for 2 week and no burst release 
      were observed in vitro and in vivo. The pharmacokinetic behavior showed that 
      higher concentration of 5-FU was found in peritoneal fluid when compared to 
      plasma, which resulted in significantly improving antitumor activity as well as 
      decreasing the side effect. It was proved that the 5-FU-implant was more 
      efficacious and much safer than 5-FU bolus injection, which would be also used to 
      overcome the reoccurrence of colon cancer after surgery.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Li, Ling
AU  - Li L
AD  - Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 
      No. 24 Tongjiaxiang, 210009 Nanjing, China; Jiangsu Simcere Pharmaceutical Co., 
      LTD, No. 699-18 XuanWu Avenue, 210042 Nanjing, China.
FAU - Li, Chao
AU  - Li C
AD  - Jiangsu Simcere Pharmaceutical Co., LTD, No. 699-18 XuanWu Avenue, 210042 
      Nanjing, China.
FAU - Zhou, Jianping
AU  - Zhou J
AD  - Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 
      No. 24 Tongjiaxiang, 210009 Nanjing, China. Electronic address: 
      zhoujianping60@163.com.
LA  - eng
PT  - Journal Article
DEP - 20180721
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Implants)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*administration & dosage/pharmacokinetics
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*drug therapy/metabolism
MH  - Delayed-Action Preparations/administration & dosage/pharmacokinetics
MH  - *Drug Implants
MH  - Fluorouracil/*administration & dosage/pharmacokinetics
MH  - Mice, Nude
MH  - Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage
MH  - Rats, Sprague-Dawley
MH  - Therapeutic Index, Drug
OTO - NOTNLM
OT  - 5-Fluorouracil
OT  - Colon cancer
OT  - Implant
OT  - Poly(lactide co-glycolide) (PLGA)
OT  - Sustained release
EDAT- 2018/07/25 06:00
MHDA- 2019/01/08 06:00
CRDT- 2018/07/25 06:00
PHST- 2018/03/30 00:00 [received]
PHST- 2018/07/04 00:00 [revised]
PHST- 2018/07/20 00:00 [accepted]
PHST- 2018/07/25 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/07/25 06:00 [entrez]
AID - S0378-5173(18)30522-2 [pii]
AID - 10.1016/j.ijpharm.2018.07.045 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 Oct 25;550(1-2):380-387. doi: 10.1016/j.ijpharm.2018.07.045. 
      Epub 2018 Jul 21.