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Sustained Delivery of IL-1Ra from Pluronic F127-Based Thermosensitive Gel Prolongs its Therapeutic Potentials

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Abstract

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-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.

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Acknowledgments and Disclosures

In vivo results presented here are not efficacy data. They can only be considered as animal-based pharmacokinetic and pharmacodynamic results.

This work was financially supported by the grant (No. 2010C13006) from the Science and Technology Department of Zhejiang Province, China.

We acknowledge the China Scholarship Council to award scholarship for PhD to Muhammad Sajid Hamid Akash and Kanwal Rehman. IL-1Ra was generously provided by Hisun Pharmaceuticals but the company was not involved in the design, conduct and/or analysis of experiments. One of the authors would like to admire his wife Kanwal Rehman for her motivation and support.

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Authors and Affiliations

  1. Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Muhammad Sajid Hamid Akash, Kanwal Rehman, Hongying Sun & Shuqing Chen

  2. College of Pharmacy, Government College University, Faisalabad, Pakistan

    Muhammad Sajid Hamid Akash

  3. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Ni Li & Jian-Qing Gao

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  1. Muhammad Sajid Hamid Akash
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  2. Kanwal Rehman
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Correspondence to Shuqing Chen.

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Akash, M.S.H., Rehman, K., Li, N. et al. Sustained Delivery of IL-1Ra from Pluronic F127-Based Thermosensitive Gel Prolongs its Therapeutic Potentials. Pharm Res 29, 3475–3485 (2012). https://doi.org/10.1007/s11095-012-0843-0

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