Development of a functional polymer scaffold for potential antitumour drug delivery applications

Abstract

Well-defined reactive polymer scaffolds are useful building blocks for a wide variety of applications ranging from nanotechnology to drug delivery. Modification of well-defined reactive polymer scaffolds via selective and efficient synthetic strategies potentially provides an easy, versatile and useful route to (multi)functional polymer structures for potential drug delivery applications. In this thesis, a homopolymer scaffold, poly(pyridyldisulfide ethylmethacrylate) (PPDSM), having pendant pyridyldisulfide (PDS) groups, was synthesised by reversible addition-fragmentation chain transfer (RAFT) polymerisation. The versatility of PPDSM as a reactive scaffold was investigated by modifying the scaffold with different thiol- and ene-compounds via highly efficient pyridyldisulfide-thiol exchange, Michael-addition or radical-mediated thiol-ene reactions. The reaction yields and the physicochemical properties of the resultant products were investigated using varying techniques. The water-insoluble PPDSM scaffold was converted to disulfide crosslinked nanoparticles simply by modifying the scaffold with hydrophilic compounds such as poly(ethylene glycol) (PEG) or a tripeptide. An antitumour drug (Doxorubicin)-conjugated, PEGylated, crosslinked nanoparticles were further synthesised directly from the PPDSM homopolymer scaffold in a one-pot Michael addition reaction. The designed physicochemical features such as the size, surface chemistry, and the in vitro drug release properties of the developed drug carrier system were assessed. The preliminary cytotoxicity and cell uptake profile of the Doxorubicin-conjugated, PEGylated nanoparticles generated from PPDSM scaffold were determined using in-vitro cultured human cervical carcinoma cell line (HeLa cells).