Recombinant polymers for drug and gene delivery

H. Ghandehari
University of Utah,
United States

Keywords: Recombinant polymers, drug and gene delivery

Summary:

One method to synthesize protein-based polymers is by recombinant techniques. This methodology provides the ability to precisely correlate structure with function in gene and drug delivery [1]. We have synthesized a series of silk-elastinlike protein polymers (SELPs) for localized adenoviral gene delivery to treat head and neck solid tumors. In these polymers matrix metalloprotease (MMPs) responsive sequences were placed at strategic locations in the backbone. Results show that control over the location of MMP responsive sequences has a profound impact on survival of head and neck tumor bearing animals treated with matrix-mediated adenoviral gene directed enzyme prodrug therapy [2-4]. These copolymers have further shown promise as liquid embolics [5] and when mixed with radioprotective agents have shown utility in the treatment of radiation-induced proctitis [6]. More recent efforts involve the fabrication and characterization of SELP nanoparticles for delivery of bioactive agents. Acknowledgements: This research was made possible by the efforts of lab members and collaborators in part listed in the references below. Support was provided by NIH grants RO1 CA107621, R42 CA168123, and F30 CA176922, and NSF GRFP 1256065. References: [1] R. Price, A. Poursaid, H. Ghandehari. Controlled release from recombinant polymers, Journal of Controlled Release, 190 (2014) 304-13. [2] J. Gustafson, R. Price, J. Frandsen, C.R. Henak, J. Cappello, and H. Ghandehari, Synthesis and characterization of matrix-metalloproteinase responsive silk-elastinlike protein polymer, Biomacromolecules, 14 (2013) 618-625. [3] R. Price, A. Poursaid, J. Cappello, H. Ghandehari, Effect of shear on physicochemical properties of matrix metalloproteinase responsive silk-elastinlike hydrogels, Journal of Controlled Release, 195 (2014) 92-8. [4] R. Price, A. Poursaid, J. Cappello, and H. Ghandehari, In vivo evaluation of matrix metalloproteinase responsive silk-elastinlike protein polymers for cancer gene therapy, Journal of Controlled Release, 213 (2015) 96-102. [5] A. Poursaid, R. Price, A. Tiede, E. Olson, E. Huo, L. McGill, H. Ghandehari*, and J. Cappello*, In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization, Biomaterials, 57 (2015) 142-52. [6] M. M. Jensen, W. Jia, K. J. Isaacson, A. Schults, J. Cappello, G. D. Prestwich, S. Oottamasathien*, H. Ghandehari*, Silk-elastinlike protein polymers enhance the efficacy of a therapeutic glycosaminoglycan for prophylactic treatment of radiation-induced proctitis, Journal of Controlled Release, 2017 Feb 20 [Epub ahead of print].