Assessment of release kinetics, stability and polymer interaction of poloxamer 407-based thermosensitive gel of interleukin-1 receptor antagonist

Abstract

Sustained delivery of proteins from polymer-based thermosensitive gel has achieved considerable attention since last decade. In our previous work, we developed a formulation for sustained delivery of IL-1Ra-loaded poloxamer 407 formulation and investigated its in vitro and in vivo characteristics. In the present work, we extended this approach to investigate stability of IL-1Ra from poloxamer 407 formulation stored at 4 °C, 25 °C and 40 °C for 3 months. Samples were taken and in vitro drug release kinetics was studied. Percent of drug content was measured using the BCA method. DSC and SDS-PAGE were used to assess the conformational stability of IL-1Ra. FTIR spectroscopy was performed to investigate the drug–polymer interaction. From the results, it was found that gelation temperature, viscosity and in vitro release pattern of IL-1Ra from poloxamer 407 formulation at 4 °C were almost same throughout the stability study period. DSC profiles of IL-1Ra loaded in poloxamer 407 formulation increased the thermostability of IL-1Ra significantly in poloxamer 407 formulation. There were no apparent changes in the entire FTIR spectrum of the IL-1Ra that would suggest that there was no effect of the polymer on the structure of IL-1Ra. Moreover, results of SDS-PAGE confirmed the stability of IL-1Ra in poloxamer 407 formulation. These results provided evidence that poloxamer 407 is a promising polymer not only for sustained delivery of IL-1Ra but also provides conformational stability for extended time.

• DSC
• FTIR
• Pluronic F127
• poloxamer 407
• stability of IL-1Ra
• sustained release of IL-1Ra

Acknowledgements

We acknowledge the China Scholarship Council to award full bright scholarships 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 Mrs. Akash for her motivation and support. Without her, the publication of this article would not have been possible.