Controlled release of bioactive IL-2 from visible light photocured biodegradable elastomers for cancer immunotherapy applications

Abstract

Biodegradable elastomeric controlled-release poly (decane-co-tricarballylate) (PDET) based matrices capable of maintaining the stability and bioactivity of Interleukin-2 (IL-2) through the utilization of visible-light curing and solvent-free loading of the cytokine are reported. The elastomeric devices were fabricated by intimately mixing lyophilized IL-2 powder with the acrylated prepolymer before photocrosslinking. The bioactivity of the released protein was assessed by its ability to stimulate the proliferation of the C57BL/6 mouse cytotoxic T lymphocyte, and its concentration was analysed using ELISA. The influence of changes in the polymer's physicochemical and mechanical properties on IL-2 release kinetics and bioactivity were also studied. The increase in the device's surface area and the incorporation of trehalose in the loaded lyophilized mix increased the IL-2 release rate with drug release proceeding via typical zero-order release kinetics. Moreover, the decrease in the degree of acrylation of the prepared devices increased the IL-2 release rate. The bioactivity assay showed that IL-2 retained over 94% of its initial bioactivity throughout 28 days of the release period. A new protein delivery vehicle composed of biodegradable PDET elastomers was demonstrated to be promising and effective for linear, constant, and sustained osmotic-driven release of bioactive IL-2 and other sensitive proteins and hormones.

Graphical Abstract

Keywords:

• Interleukin-2
• biodegradable elastomer
• photopolymerization
• osmotic release
• protein stability
• cancer therapy

Acknowledgments

Open Access funding provided by the Qatar National Library. The support of the Central Lab Unit team at Qatar University is highly appreciated. Some of the experiments were supported by NSERC discovery funds granted to HY.

Author contributions

Conceptualization & funding acquisition, HY; methodology, MS, JD and HY; validation, MS and HY; investigation, MS and HY; resources, HY; data curation, MS; writing of original draft preparation, MS and HY; review and editing, HY; visualization, MS and HY; supervision, HY; project administration, HY; All authors have read and agreed to the published version of the manuscript. This research work has been partially built on the technology reported in US Patent Number. US9422396B2 granted to HY.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This project was made possible by NPRP 09 − 969 − 3 − 251 from Qatar National Research Fund (a member of Qatar Foundation) through its National Priorities Research Program granted to H. Younes. The statements made herein are solely the responsibility of the authors. Mohamed Shaker was a Ph.D. student at MUN with fund support from the Arab Republic of Egypt.