Study of the physico-chemical properties of macromolecular assemblies

Abstract

Block copolymers are a diverse group of macromolecules that have attracted a great deal of attention due to their ability to self-assemble into a variety of nanostructures. These nanostructures can be tuned over a wide range of morphologies and hence can be used in a plethora of applications ranging from delivery platforms for drugs and genes to nanosized reactors. Block copolymers, primarily used for drug delivery applications, consist of at least one hydrophobic and one hydrophilic polymer chain that are covalently linked to one another. There are many factors that play a role in determining the morphology of the self-assembled molecule for example, the nature and length of the polar hydrophilic group, the length of the hydrophobic polymer, temperature and the type of common solvent employed during the self-assembly. The first project involved the synthesis and self-assembly of micelles using amphiphilic blocks copolymers like polyethylene glycol (PEG) and polycaprolactone (PCL) with different PEG and PCL lengths. These polymers showed good correlation between the molecular weights obtained from gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). We next demonstrated that by varying the individual components of the block copolymers, we could systematically change the micelles’ physico-chemical property like size. The study of the corresponding micelles showed that there was a slight increase in size with the increase of hydrophobic, PCL length, while a significant increase in the size was observed with the decrease of hydrophilic - PEG length. A single study on a selected PEG-PCL polymeric micelle using atomic force microscopy (AFM) analysis and click chemistry revealed the force required to destabilize the micelles by pulling the single polymer chain is 47pN. The next study involved replacing the hydrophilic PEG with a sugar moiety and conducting similar study on the relationship of the block length and molecular weight on the morphology of the micelles. The synthesis of the polysaccharide based block copolymers was done by employing the copper-(I)-catalyzed azide-alkyne cycloaddition. It was observed that when lactose was used as the hydrophilic block, the micelles obtained were unstable. Synthesis of higher sugar analogues was proposed using Lewis acid mediated acetolysis of -cyclodextrin. However, attempts to further modify the polysaccharide were futile and the synthesis of the higher analogues is still underway.