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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Antirheumatic Agents, Delayed-Action Preparations, Electrophoresis, Polyacrylamide Gel, Gels, Interleukin 1 Receptor Antagonist Protein, Interleukin-1beta, Interleukin-6, Male, Poloxamer, Protein Stability, Rats, Rats, Wistar, Temperature.
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Does sustained delivery of IL-1Ra from pluronic F127-based thermosensitive gel prolong its therapeutic potentials? Context: 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). 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. 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.
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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. Final Decision: yes