Preserving Therapeutic IL-2 Stability and Bioactivity: A Novel Controlled Release Polymeric Drug Delivery Approach

Abstract

Abstract Introduction: The application of therapeutic proteins and cytokines like Interleukin-2 (IL-2) for long-term, localized delivery has been hindered by a lack of a delivery device that releases active protein at a concentration within their therapeutic window. The purpose of this oral presentation is to report on the osmotic-driven, controlled-release from novel visible-light photocrosslinked biodegradable elastomeric devices recently designed in an attempt to overcome this limitation. Materials and Methods: All chemicals were purchased from Sigma-Aldrich and used as received. Novel biodegradable and biocompatible poly (decaneco- tricarballylate) [PDET] elastomers were synthesized by polycondensation reaction between tricarballylic acid and alkylene diols, followed by acrylation and photo-curing. IL-2 loaded micro-cylinder and disk-shaped elastomeric devices were prepared by intimately mixing IL-2 lyophilized powder with the acrylated prepolymer prior to photocrosslinking. IL-2 release was analysed using IL-2 ELISA system and the in vitro bioactivity of released IL-2 was assessed using C57BL/6 mouse cytotoxic T lymphocyte. The influence of various parameters such as the elastomer crosslinking density, the volumetric drug loading percentage and the incorporation of osmotic excipients like trehalose on the release kinetics of the drug was also examined. Results and discussion: The disk-shaped specimens showed faster IL-2 release profiles than microcylinders, with drug release proceeding via typical zero-order release kinetics. The increase in the device's surface area and the incorporation of trehalose in the loaded lyophilized mix increased the IL-2 release rate. As well, it was shown that the decrease in the degree of prepolymer acrylation of the prepared devices increased the IL-2 release rate. Cell based bioactivity assays showed that IL-2 released over a period of 28 days, retained more than 94% of its initial activity. These bioactivity results represent a highly significant improvement over the other previously published data provided with a quantitative analysis of the actual percentage of bioactive IL-2 released during the period of the release study. Conclusion: The novel PDET elastomeric drug delivery systems demonstrated to be promising as protein drug delivery vehicles for localized and sustained IL-2 immunotherapy. Acknowledgements: Work is supported by QNRF through the NPRP grant # 09-969-3-251 awarded to HM Younes.