Design and Developement of Biodegradable Zwitterionic Polymers for Drug Delivery in Cancer

Abstract

Zwitterionic polymers are well known for their wide range of biomedical applications such as drug delivery, protein conjugation, nanoparticle formation, etc. This thesis is aimed at “Designing and Developing Enzymatically Biodegradable Zwitterionic Block Copolymers for Drug Delivery in Cancer.” For this purpose, two γ-substituted caprolactone monomers were tailor-made by multi-step organic synthesis. Ring-opening polymerization (ROP) technique was employed to achieve linear, and star (6-arm) shaped block copolymer based several architectures. Further, linear and star polymers were post-modified to yield cationic, anionic and zwitterionic amphiphilic structures. The chain length in linear and each arm of star architecture is kept same to understand the role of topology. Monomers and polymers were characterized using 1H NMR, 13C NMR, FT-IR, mass spectra. The molecular weight of polymers was estimated using Gel Permeation Chromatography (GPC). Thermal properties were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The polymers were found to be stable up to 250 ℃ and semicrystalline to amorphous in nature. Self-assembly in aqueous medium showed formation of aggregated nano assembles having hydrodynamic diameter in the range of 60-340 nm for linear polymers and 30-200 nm for star polymers. pH dependent size and zeta potential measurements revealed formation of stable nano-assemblies. HPTS (biomarker) dye was encapsulated in the linear and star zwitterionic with excellent dye loading capacities of 3%. HPTS loaded nanoparticles were characterized for size and zeta potential analysis.