All ETDs from UAB

Advisory Committee Chair

Eugenia Kharlampieva

Advisory Committee Members

Aaron Lucius

Claudiu Lungu

Derrick Dean

James Patterson

Document Type

Dissertation

Date of Award

2017

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

The research presented in this thesis is focused on the design and development of stimuli-responsive polymeric particles for drug delivery, including tannic acid-based layer-by-layer capsules with pH- and ionic strength-dependent permeability as well as size- and structure-tunable poly-(N-vinylcaprolactam)-based temperature-responsive polymersomes and micelles. Polymer-based particles play essential roles in controlled drug delivery due to their tunable sizes and nanostructures, and can be further advanced through functionalization, allowing pH-, ionic strength- and temperature-sensitivities to alter the therapeutics’ pharmacokinetics and bio-distribution. Two typical pathways for engineering polymeric drug delivery vehicles are introduced in this thesis, layer-by-layer self-assembly at inter-faces and self-assembly from block copolymers solutions. In Chapter two, tannic acid/poly(N-vinyl pyrrolidone) (TA/PVPON) hydrogen bonded films and capsules were fabricated and loaded with the hydrophobic anticancer drug doxorubicin (DOX). The pH- and ionic strength-dependent ionization degree of TA allows precise control of the film thickness as well as the permeability after being self-assembled with PVPON by hydrogen bonding. The hydrophobic therapeutic doxorubicin (DOX) can be loaded into the novel TA/PVPON capsules with high loading capacity at 1.41×10-3 ng of DOX per capsule at both pH 7.4 and 5 for long term storage. In Chapter three, novel temperature-sensitive polymersomes from poly(-N-vinylcaprolactam)n-poly(dimethylsiloxane)65-poly(-N-vinylcaprolactam)n (PVCLn-PDMS65-PVCLn) triblock copolymers were investigated. The chain length of the temper-ature-responsive component PVCL was accurately controlled by using RAFT controlled polymerization and the polymersome structure was modulated by adjusting the hydro-philic content ratio. Reversible temperature-sensitive size and permeability changes of fabricated polymersomes were observed from 25 to 55 °C. Hydrophilic doxorubicin hy-drochloride (DOX HCl) can be loaded into synthesized polymersomes with precisely controlled temperature-dependent release. Further, Dox-loaded polymersomes exhibit both concentration- and time-dependent cytotoxicity for human alveolar adenocarcinoma cells. In Chapter four, novel duel temperature-responsive micelles from poly(3-methyl-N-vinylcaprolactam-co-vinylcaprolactam)-b-poly(vinyl caprolactam-co-vinyl pyrrolidone) diblock copolymer were studied. Novel monomer 3-methyl-N-vinylcaprolactam was synthesized and utilized to form block copolymers in order to achieve structural ho-mogeneity. The synthesized amphiphilic block copolymer can self-assembly into micelles at room temperature with two LCSTs. The first LCST was found to be between 19 to 27 °C and can be used to load the hydrophobic drug DOX and form micelles. The second LCST is controlled between 41 and 42 °C caused micelles aggregation and therefore can be useful in achieving targeting functionality for pathological tissues that have elevated temperatures.

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