Grant: Discovery Grants Program - Individual

This research program focuses on the development of advanced nanocarriers for nanomedicines. The development of novel nanocarriers and their significant contribution in drug delivery applications is directly related to the progress of researchers in field of polymer chemistry. The synthesis of novel cationic polymers and nanoparticles with improved gene delivery efficacies are one example of such nanocarriers. The significant success of synthetic nanocarriers in field of nanomedicines encouraged us to design a novel multifunctional platform of polymeric vectors with potent antibacterial and gene and drug delivery efficacies. Our proposed platform of polymeric carriers is composed of two main components; a) novel biocompatible moiety with antibacterial properties and b) multiple amine containing cationic moieties of linear and branched architectures. Biomolecules functionalized polymeric carriers are well-studied to impart biocompatibility to synthetic vectors. Among biomolecule-functionalized materials, synthesis of vitamin based materials are uncommon and only handful of reports discuss the used of vitamin B5 based materials for tissue engineering applications. Vitamin B5 is a water-soluble molecule and is an important component of mammalian and bacterial metabolism. The slight changes in structure of vitamin B5 are known to cause lethal impact on bacterial viability, with no significant changes in mammalian cell viability. Owing to these multifunctional attributes of vitamin B5 based materials, we argue that vitamin B5 based polymeric vectors will be ideal polymeric carriers with simultaneous antibacterial and gene and drug delivery capabilities. Similarly, the choice of cationic component is a critical factor for success of our materials. The research on gene delivery capabilities of cationic polymers reveals that physiochemical properties of cationic vectors largely dictate their biological outcomes (such as toxicity and gene delivery efficacies). Polyethyleneimine (PEI) is a well-known gene delivery vectors, which is composed of primary, secondary and tertiary amines and combination of these amines in PEI is found to enhance the gene expression of this polymer. To the best of our knowledge, polymerization of multiple amine containing cationic monomers by reversible addition fragmentation chain transfer (RAFT) polymerization is not yet reported. In order to develop multifunctional nanocarriers, we aim to prepare vitamin B5 analogous monomer and multiple amine containing RAFT active monomers of linear and branched architectures followed by their homo and copolymerization by RAFT approach to yield well-defined polymers and nanoparticles of predetermined molecular weight, architecture and compositions. The platforms of polymers obtained will be tested for their gene and drug delivery efficacies and antibacterial properties during in vitro studies.