Sustained delivery of IL-1Ra from pluronic F127-based thermosensitive gel prolongs its therapeutic potentials.
OBJECTIVE
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-1β-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-1β-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.
Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Muhammad Sajid Hamid
MS
Akash
Kanwal
K
Rehman
Ni
N
Li
Jian-Qing
JQ
Gao
Hongying
H
Sun
Shuqing
S
Chen
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005782:Gels / Q000737:chemistry; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D020442:Poloxamer / Q000737:chemistry*; D055550:Protein Stability; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D000093242:Interleukin-6 Inhibitors
D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D005782:Gels; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D020442:Poloxamer; D000093242:Interleukin-6 Inhibitors