Event Abstract Back to Event Micellar delivery of paclitaxel using a glucosamine-based glycopolymer for the treatment of prostate cancer Alice Du1, Hongxu Lu2 and Martina H. Stenzel2 1 University of New South Wales, Centre for Advanced Macromolecular Design, School of Chemical Engineering, Australia 2 University of New South Wales, Centre for Advanced Macromolecular Design, School of Chemistry, Australia Introduction: The use of carbohydrates in the synthesis of polymeric nanoparticles has garnered interest in recent years, especially for its potential use as a therapeutic delivery vehicle for cancer treatment. For example, recent work reported by our group utilised the natural targeting ability of fructose decorated micelles for the treatment of triple-negative breast cancer[1]. Another carbohydrate of note is chitosan, a glucosamine-based glycopolymer which has shown potential in oral delivery approaches. However, one of the major disadvantages of chitosan lies in the handling difficulty of the macrostructure and control over its molecular weight. Hence, it is the aim of this study to synthesize a glucosamine monomer which is capable of undergoing controlled polymerization. Subsequent drug loading, micelle formation and in vitro studies will be used to evaluate the efficacy of the glycopolymer micellar system as a delivery vehicle for the treatment of prostate cancer. Materials and Methods: The solubility of glucosamine in organic solvents was increased through protection of its hydroxyl and amino functional groups. 2-hydroxyethyl acrylate was used to introduce alkene functionality to afford the protected glucosamine monomer (GluHEA). The polymerisation of GluHEA was controlled using a reversible addition-fragmentation chain transfer (RAFT) agent and subsequent chain extension was completed using 2-carboxyethyl acrylate (CEA). Paclitaxel was chemically conjugated to the CEA block and used to introduce hydrophobicity to the block. Deprotection of the glucosamine will then afford the hydrophilic block, thereby inducing micelle formation. In vitro biological studies will be conducted where the toxicity of the micelles will be evaluated against both monolayer cell culture as well as multicellular tumor spheroids. In addition, the migratory ability of the glucosamine-coated nanoparticles through Caco-2 (epithelial) cells will be investigated and compared to chitosan. Results: Synthesis of PGluHEA26-b-PCEA64 was successfully completed and controlled using 3-(benzylsulfanylthiocarbonyl sulfanyl)-propionic acid (BSPA) as the RAFT chain transfer agent (polydispersity ~1.3). Subsequent conjugation of paclitaxel to the carboxylic acid groups on the PCEA block was also successful. Conclusion: It is envisioned that the glucosamine coated micelles will offer a viable alternative to chitosan as an enhanced transcell delivery vehicle. In addition, the synthesis of a glucosamine monomer allows the structure of the block copolymer to be finely controlled, a characteristic not associated with naturally derived chitosan.