Research Projects

The remarkable success of RNA vaccines in combating many diseases including Coronavirus diseases establishes that nucleic acids are the drugs of the future and potential alternatives to conventional vaccine therapy. The targeted drug delivery is also the key to afford efficient delivery and better therapeutic response for curing genetic and acquired diseases without nominal side effects on other healthy parts. But, these are dependent on the development of safe and efficient carriers, which further rely on the design and synthesis of new bioinspired polymeric materials via new synthetic approaches for drug and gene deliveries. Cationic poly(ethylene imine) (PEI), functionalized polypeptides and other polymers, owing to their high transfection efficiencies, have been used as a non-viral gene carrier. However, the charged PEI and other polymers suffers from significant toxicity issues as well as poor blood compatibility and the charged synthetic polypeptides requires stringent and lengthy reaction process. In the field of targeted delivery of drug molecules and nucleic acid therapeutics, pseudopeptidic poly(2-oxazoline)s (POxs) is emerging as a promising alternative due to the ease of functionalization, ability to generate diverse amphiphilic copolymeric architectures, structure variability and biocompatibility. Despite this potential, the utilization of cationic POxs and POxs-based amphiphilic block copolymer (ABCP) remains relatively unexplored for potential drug and gene delivery applications. In this proposed research, poly(2-oxazoline)s (POxs) and their ABCP with diverse structure versatility and controllable charge density after cationization are fabricated for targeted nucleic acid and drug delivery. To achieve this, several different 2-oxazoline monomers such as Boc-protected proline oxazoline (Boc-ProOx), pentenyl-2-oxazoline (pentenylOx), Boc-protected glutamic acid oxazoline (Boc-GluOx), and Boc-protected 4-aminobutanoic acid oxazoline (Boc-ButOx) will be designed and synthesized starting from different amino acids and other organic acid precursors. In order to vary the nature of oxazoline monomer, it is also planned to synthesize oxazoline monomers from 5-hexenoic acid (HAOx) for size-chain modification and methyl mercapto alkanoic acid (MMAA) for easy cationization through sulphur atom. Cationic ring-opening polymerization (CROP) of these monomers, followed by diverse post functionalization techniques will be utilized for preparing different cationic POx-based random/block copolymers. The part of this proposal will be focused on the study of stimuli-responsiveness of these cationic polymers under different stimuli such as temperature, pH, ions, ionic strength, etc in aqueous solution. The aim is also to study of self-assembly of POxs-based ABCP into nanostructures of various shapes and their applications in stimuli-tiggered drug delivery. It is planned to test the transfection efficiency at various N/P ratios of glycosylated cationic POx copolymers, hydroxyl-rich cationic poly(2-oxazoline) with galactose units, amphiphilic POx copolymers containing ionizable guanidine moieties and cationic MMAA-based POxs. Their cytotoxicity, condensation ability and transfection efficiency will be accessed into various cell lines. Finally, these cationic POx with tailored structures and tunable charge densities will be utilized for targeted nucleic acid delivery to specific cell lines. The completion of the project will unveil the potential of these cationic POXs not only for the targeted delivery of nucleic acid therapeutics but also for broader applications in drug delivery and tissue engineering.