DESIGN, SYNTHESES, AND PROPERTIES OF TUNABLE, DUAL-STIMULI (TEMPERATURE AND pH) RESPONSIVE COPOLYMERS

Open Access
- Author:
- Manokruang, Kiattikhun
- Graduate Program:
- Materials Science and Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 07, 2010
- Committee Members:
- Evangelos Manias, Dissertation Advisor/Co-Advisor
Evangelos Manias, Committee Chair/Co-Chair
Qing Wang, Committee Member
Michael A Hicker, Committee Member
Peter J Butler, Committee Member
Gary Lynn Messing, Committee Member - Keywords:
- alternating copolymers
aqueous phase behavior
phase diagram
hydrogel
stimuli responsive polymers
polyurethane
water soluble polymers
Lower Critical Solution Temperature (LCST)
microcapsules
segmented block copolymers
multicompartment micelles - Abstract:
- Stimuli responsive polymers are of great interest in biorelated applications ranging from actuators, microfluidics, delivery systems and tissue scaffolds. The specifications of an appropriate polymer system that shows a response to one or more external stimuli vary from application to application, depending on desired functionality. In most cases, the response to an environmental change is desired to be sharp and fast, such as for microfluidics and actuators, while the stability of the collapsed structure is also typically required, such as in tissue scaffolds and in stimulated delivery systems. In addition, the onset of the stimulus response varies depending on application. Thus, a general design strategy for polymer systems to meet specific applications’ needs can be a big challenge. This dissertation describes the design, syntheses, and aqueous phase behavior of two polymer classes that show a sharp solution phase transition in different manners: The first polymer class is in the form of a segmented/blocky copolymer and its solution phase separation is designed to occur via micellization, while the second polymer class is designed as an alternating copolymer and it exhibits a first order LCST phase behavior. Copolymers of methyl methacrylate (MMA) and methacrylic acid (MAA), poly(MMA-co-MAA)s, were prepared to have a segmental blocky comonomer distribution along the chain backbone, with sequences composed predominantly of MMA or MAA units. Turbidity (cloud point) measurements were employed to investigate the phase behavior of these copolymers in aqueous solution. The solutions showed sharp solubility transitions upon pH change, and the pH-onsets of the copolymers’ transition showed a systematic dependence on the copolymers’ MAA content and an almost-linear dependence on the polymer concentration. A strong hysteresis was observed when lowering versus increasing pH, indicating a stable collapsed structure. Dynamic light scattering demonstrated almost monodispersed polymer aggregates for each pH, rather than random/polydisperse structures. TEM images of the collapsed morphology showed polymer aggregates that included numerous small hydrophobic cores, demonstrating that the phase transition of these copolymers involved the formation of micelles with many hydrophobic clusters. Finally, these copolymers were used to prepare hollow microcapsules that provided an exceptional protection and a prolonged stability of an encapsulated matter at acidic conditions (pH 2) and a sharp and fast pH-triggered release at physiological conditions (pH 7). A second series of copolymers was synthesized to compose of ethylene glycol oligomers (EOm) connected in an alternating fashion with hydrophobic alkyls (EEn), (EOm-alt-EEn). Also, terpolymers were synthesized to compose of EOm connected in an alternating fashion with EEn and lysine ethyl ester (LyE), (EOm-alt-(EEn;LyE). Both copolymers and terpolymers demonstrated temperature responsive LCST phase behavior in aqueous solution, whose critical temperature is dictated by the thermodynamics of the hydrophilic/hydrophobic balance. In addition, the terpolymers’ LCST can be further tuned by tailoring the ratio of EEn to LyE yielding dual responsive, viz. temperature and pH responsive, polymers upon conversion of LyE to ionizable Lysine (Lys). These last polymers that included ionizable units showed a reversible temperature and pH sensitive phase transition, allowing for such polymers to exhibit a phase separation with both-or-either temperature increase and pH-decrease. The extended phase diagrams, collected from turbidity measurements and modulated differential scanning callorimetry (MDSC), showed that the phase diagram remained a genuine LCST binodal throughout the complete concentration range. In addition, 1H-NMR provided additional strong evidence that the phase transition proceeded without micelle formation. Finally, hydrogels were prepared from EOm-alt-EEn, which exhibited reversible swelling/deswelling during temperature cycling (albeit with strong kinetic signatures). These temperature responsive hydrogels may be used in biomedical applications such as a rate-controlled swelling device.