Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2015

Month Degree Awarded

February

First Advisor

Sankaran Thayumanavan

Subject Categories

Materials Chemistry | Medicinal-Pharmaceutical Chemistry | Organic Chemistry | Polymer Chemistry

Abstract

Supramolecular nanoassemblies capable of reducing non-specific interactions with biological macromolecules, such as proteins, are of great importance for various biological applications especially for targeted drug delivery therapeutics. Recently, zwitterionic materials have been shown to reduce non-specific interactions with biomolecules, owing both to their charge neutrality and their ability to form strong hydration layer around zwitterions via electrostatic interactions. This dissertation focuses on design, synthesis, thorough characterization, and applications of zwitterionic amphiphilic dendrimers and polymeric materials. Firstly, A new triazole-based zwitterionic moiety was conceived and incorporated as the hydrophilic functionality in facially amphiphilic dendrons. Self-assembly characteristics and the structural and functional characteristics of the zwitterionic dendrons were then evaluated by spectroscopic techniques and by comparison with the corresponding charge-neutral PEG and anionic carboxylate-based dendrons respectively. Surface charge measurements, temperature sensitivity and evaluation of interactions of these assemblies with proteins form the bases for these comparisons. Because of the charge neutral characteristics of zwitterionic moieties exposed to outer aqueous phase, these dendritic assemblies evade non-specific interactions with biological milieu while enhancing the responsiveness towards specific biological triggers, such as proteins. We further simplified this molecular design by developing synthetically accessible zwitterionic carboxybetaine based amphiphilic polymers. Zwitterionic amphiphilic polymers are synthesized in a simple one-pot reaction by treating reactive acrylate polymer with secondary amine and 2-bromoaceticacid. This zwitterionic polymer possesses hydrophilic glycinebetaine and hydrophobic decyl chains placed orthogonally and forms environment dependent self-assembled aggregates owing to its amphiphilicity. The zwitterionic assemblies stably encapsulate guest molecules and undergo pH-dependent zeta potential and size variations owing to the pH sensitivity of zwitterionic component. In a related project, we’ve developed degradable polycarbonate based amphiphilic polymers possessing hydrophilic peg and hydrophobic decyl components. This degradable polymers form self-assembled aggregates encapsulate hydrophobic guest molecules, undergo degradation upon changes in pH or in presence of enzymes (PLE, an esterase). Work is underway towards the design and synthesis of zwitterionic amphiphilic degradable polymers and their characterization. Over all the work presented in this thesis have implications in design and development of polymeric excipients for targeted drug delivery, controlled release of drugs, and stimuli-sensitive therapeutics.

Share

COinS