Linear and star block copolymer nano architectures for drug delivery

Abstract

Conventional chemotherapeutic clinical drugs are predominantly small molecules and they have many limitations such as poor biodistribution lacking target specificity short half life and consequential side effects like cardiotoxicity nephrotoxicity and neurotoxicity etc This obstacle in cancer treatment led to the development of 8220 polymer therapeutics 8221 that offer the advantage of passive selectively targeting the tumor tissue via the enhanced permeability and retention EPR effect Herein aliphatic polyesters seem to have gained impetus as polymeric drug delivery vehicles owing to their biodegradability facilitated by enzymes at the intracellular compartments especially paving way for the environmentally stable and structurally tunable polycaprolactone PCL based scaffolds The underlying principle of the thesis is to engineer amphiphilic fully biodegradable PCL nano scaffolds and investigate the impact of polymer architecture on macromolecular self assembly along with the ability to cross biological barriers In this thesis work new classes of amphiphilic linear block and random copolymers were developed via ring opening polymerization of 949 caprolactone and tailor made 611 carboxylic substituted caprolactone The difference in polymer topologies manifested in their solid state assemblies wherein the block copolymers were semi crystalline in nature as opposed to the amorphous random copolymers Their aqueous self assemblies resulted in the formation of stable spherical nanoparticles with excellent loading capability of anticancer drug doxorubicin DOX in the hydrophobic pocket These polymer scaffolds were found to be stable under physiological conditions and the in vitro release kinetics revealed selective rupturing in the presence of lysosomal esterase enzyme to deliver DOX at the intracellular compartment The cytotoxicity study exhibited that the nascent polymers were highly biocompatible whereas the DOX loaded nanoparticles resulted in gt 90 cell death Further efforts have been taken to tweak the p