PMID- 22907416
OWN - NLM
STAT- MEDLINE
DCOM- 20130422
LR  - 20211021
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Linking)
VI  - 29
IP  - 12
DP  - 2012 Dec
TI  - Sustained delivery of IL-1Ra from pluronic F127-based thermosensitive gel 
      prolongs its therapeutic potentials.
PG  - 3475-85
LID - 10.1007/s11095-012-0843-0 [doi]
AB  - PURPOSE: Pluronic F-127 (PF127) has previously shown to prolong the sustained 
      release of various proteinous drugs and their serum half-lives. Subsequently, we 
      have extended this approach to look at in vitro release, in vivo efficacy and 
      pharmacokinetics of interleukin-1 receptor antagonist (IL-1Ra). METHODS: Various 
      concentrations of PF127 gels were prepared using cold method. In vitro drug 
      release kinetic studies were performed using membraneless dissolution method. 
      Stability of IL-1Ra was assessed by SDS-PAGE. In vivo studies and in vivo 
      bioactivity of IL-1Ra were also performed on wistar rats. RESULTS: IL-1Ra loaded 
      PF127 gels showed in vitro sustained release of IL-1Ra, depending on the 
      concentration of gel used. SDS-PAGE confirmed the stability of protein during its 
      in vitro release. PF127 gel also exhibited prolonged release of IL-1Ra in rats as 
      compared to that of IL-1Ra aq. solution. In vivo bioactivity of IL-1Ra loaded in 
      gel was confirmed by its ability to inhibit IL-1beta-stimulated induction of IL-6. 
      CONCLUSIONS: When compared directly, IL-1Ra loaded PF127 gel exhibited prolonged 
      in vitro and in vivo release, greater efficacy to induce hypoglycemia and 
      inhibited IL-1beta-stimulated production of IL-6 as compared to IL-1Ra aq. solution. 
      We believe that this methodology for sustained delivery of IL-1Ra probably be 
      suitable for the convenience of patients to achieve desired therapeutic 
      potentials without exceeding dose limits and frequent administration.
FAU - Akash, Muhammad Sajid Hamid
AU  - Akash MS
AD  - Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics College of 
      Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Rehman, Kanwal
AU  - Rehman K
FAU - Li, Ni
AU  - Li N
FAU - Gao, Jian-Qing
AU  - Gao JQ
FAU - Sun, Hongying
AU  - Sun H
FAU - Chen, Shuqing
AU  - Chen S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120821
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Gels)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 106392-12-5 (Poloxamer)
SB  - IM
MH  - Animals
MH  - Antirheumatic Agents/*administration & dosage/*pharmacokinetics/pharmacology
MH  - Delayed-Action Preparations/*chemistry
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Gels/chemistry
MH  - Interleukin 1 Receptor Antagonist Protein/*administration & 
      dosage/*pharmacokinetics/pharmacology
MH  - Interleukin-1beta/immunology
MH  - Interleukin-6/antagonists & inhibitors/immunology
MH  - Male
MH  - Poloxamer/*chemistry
MH  - Protein Stability
MH  - Rats
MH  - Rats, Wistar
MH  - Temperature
EDAT- 2012/08/22 06:00
MHDA- 2013/04/23 06:00
CRDT- 2012/08/22 06:00
PHST- 2012/01/11 00:00 [received]
PHST- 2012/07/30 00:00 [accepted]
PHST- 2012/08/22 06:00 [entrez]
PHST- 2012/08/22 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
AID - 10.1007/s11095-012-0843-0 [doi]
PST - ppublish
SO  - Pharm Res. 2012 Dec;29(12):3475-85. doi: 10.1007/s11095-012-0843-0. Epub 2012 Aug 
      21.