Controlled radical polymerisation also known as reversible deactivation radical polymerisation (RDRP) has shown to be amenable to producing macromolecular constructs, with well defined polymer chain ends as well as narrow molar mass distributions. In particular, atom transfer radical polymerisation (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerisation have facilitated the synthesis of homogeneous polymers for drug delivery applications. Recently, the polymerisation techniques have also been employed to create tethered prodrug payloads that can be trafficked to the tumour tissue.
We have employed RAFT polymerisation to synthesise a range of water-soluble copolymers that consist of antiviral prodrug pendents that can be released through the triggered degradation of a self-immolative linker. We have shown that copolymers are capable of releasing a range of drugs and achieved synergistic potencies that are superior to the unmodified drugs, demonstrating the benefits of combination therapeutic systems.
We believe the fundamental design principles described here could be applied to facilitate development of polymers that promote effective and triggered delivery of an array of inhibitors that counteract other devastating diseases such as cancer, viral infections or bacterial infections.
CSIRO is continuing to develop this technology and is looking for:
- Investors & Partners – The biomedical market continues to innovate and grow. CSIRO is interested to talk to partners looking to strategically invest in new biomedical start-ups.
- Antiviral macromolecular prodrug carriers – Emerging Polymer Technologies Summit, Melbourne, 22-24 Nov 2017. [ddownload id=”433″ style=”link”]
- “Triple Activity of Lamivudine Releasing Sulfonated Polymers against HIV-1” Danial, M., Andersen, A. H. F., Zuwala, K., Cosson, S., Riber, C. F., Smith, A. A. A., Tolstrup, M., Moad, G., Zelikin, A. N., & Postma, A. Mol. Pharmaceutics, 2016, 13, 2397-2410. doi: 10.1021/acs.molpharmaceut.6b00156.
- “Disulfide conjugation chemistry: a mixed blessing for therapeutic drug delivery?” Danial, M., & Postma, A. Ther. Delivery, 2017, 8, 359-362. doi: 10.4155/tde-2017-0003.
- “Combination anti-HIV therapy via tandem release of prodrugs from macromolecular carriers” Danial, M., Telwatte, S., Tyssen, D., Cosson, S., Tachedjian, G., Moad, G., & Postma, A. Polym. Chem., 2016, 7, 7477-7487. doi: 10.1039/c6py01882c.
- “Vaccine delivery: where polymer chemistry meets immunology” Shae, D., Postma, A., & Wilson, J. T. [10.4155/tde-2016-0008]. Ther. Delivery, 2016, 7, 193-196. doi: 10.4155/tde-2016-0008.
- “Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV” Smith, A. A. A., Zuwala, K., Kryger, M. B. L., Wohl, B. M., Guerrero-Sanchez, C., Tolstrup, M., Postma, A., & Zelikin, A. N. [10.1039/C4SC02754J]. Chem. Sci., 2015, 6, 264-269. doi: 10.1039/c4sc02754j.
- “Polymers Fight HIV: Potent (Pro)Drugs Identified Through Parallel Automated Synthesis” Zuwala, K., Smith, A. A. A., Postma, A., Guerrero-Sanchez, C., Ruiz-Sanchis, P., Melchjorsen, J., Tolstrup, M., & Zelikin, A. N. [10.1002/adhm.201400148]. Adv. Healthcare Mater., 2015, 4, 46-50. doi: 10.1002/adhm.201400148.
- “Macromolecular Prodrugs of Ribavirin: Concerted Efforts of the Carrier and the Drug” Smith, A. A. A., Wohl, B. M., Kryger, M. B. L., Hedemann, N., Guerrero-Sanchez, C., Postma, A., & Zelikin, A. N. Adv. Healthcare Mater., 2014, 3, 1404-1407. doi: 10.1002/adhm.201300637.