5 research outputs found
Tuning Sol-Gel Phase Diagrams of Doubly Thermosensitive Hydrophilic Diblock Copolymers in Water
This dissertation presents the synthesis of stimuli-responsive hydrophilic diblock copolymers and the study of their behavior in water under various conditions. The polymers were made by âlivingâ/controlled radical polymerization. Chapter 1 presents a background of this dissertation. Chapters 2-4 describe a family of doubly thermosensitive diblock copolymers with a small amount of carboxylic acid groups incorporated into either one or both blocks. The lower critical solution temperature (LCST) of the weak acid-containing block increases with increasing pH due to the ionization of carboxylic acid. Chapter 5 presents the preparation of pH-sensitive diblock copolymer micelle-embedded agarose hydrogels.
Chapter 2 describes the synthesis and solution behavior of poly(methoxytri(ethylene glycol) acrylate-co-acrylic acid)-b-poly(ethoxydi(ethylene glycol) acrylate) (P(TEGMA-co-AA)-b-PDEGEA)). PTEGMA and PDEGEA are thermosensitive polymers with LCSTs of 58 and 9 °C [degree Celsius], respectively, in water. A 20 wt% aqueous solution of P(TEGMA-co-AA)-b-PDEGEA with pH of 3.11 underwent transitions from a free-flowing liquid, to a free-standing gel, to a hot liquid, and to a cloudy mixture upon heating. The Tsol-gel [sol-to-gel transition temperature] and Tgel-sol [gel-to-sol transition temperature] are closely related to the LCSTs of the two blocks. Upon raising pH, the Tgel-sol increased, while the Tsol-gel remained the same. Accordingly, only the upper boundary of the sol-gel phase diagram shifted upward.
Chapter 3 presents the tuning of Tsol-gel of moderately concentrated aqueous solutions of doubly thermosensitive diblock copolymers by incorporating a small amount of AA groups into the lower LCST block and changing the solution pH. The AA content had a significant effect on the pH dependence of Tsol-gel. Chapter 4 shows that by incorporating a small amount of carboxylic acid groups into both blocks of a doubly thermosensitive diblock copolymer, the C-shaped sol-gel phase diagram can be readily and reversibly shifted by changing the solution pH.
Chapter 5 presents the fabrication of pH-sensitive diblock copolymer micelle-embedded agarose hydrogels. The gel properties were not significantly affected by the incorporation of the micelles even when the polymer concentration reached 5 mg/g. The pH-induced release of the payload from the core of micelles in a hybrid gel was studied. Chapter 6 presents conclusions and future work
Tuning of Thermally Induced Sol-to-Gel Transitions of Moderately Concentrated Aqueous Solutions of Doubly Thermosensitive Hydrophilic Diblock Copolymers Poly(methoxytri(ethylene glycol) acrylate)-<i>b</i>-poly(ethoxydi(ethylene glycol) acrylate-<i>co</i>-acrylic acid)
We report in this article a method to tune the sol-to-gel
transitions
of moderately concentrated aqueous solutions of doubly thermosensitive
hydrophilic diblock copolymers that consist of two blocks exhibiting
distinct lower critical solution temperatures (LCSTs) in water. A
small amount of weak acid groups is statistically incorporated into
the lower LCST block so that its LCST can be tuned by varying solution
pH. Well-defined diblock copolymers, polyÂ(methoxytriÂ(ethylene glycol)
acrylate)-<i>b</i>-polyÂ(ethoxydiÂ(ethylene glycol) acrylate-<i>co</i>-acrylic acid) (PTEGMA-<i>b</i>-PÂ(DEGEA-<i>co</i>-AA)), were prepared by reversible additionâfragmentation
chain transfer polymerization and postpolymerization modification.
PTEGMA and PDEGEA are thermosensitive water-soluble polymers with
LCSTs of 58 and 9 °C, respectively, in water. A 25 wt % aqueous
solution of PTEGMA-<i>b</i>-PÂ(DEGEA-<i>co</i>-AA)
with a molar ratio of DEGEA to AA units of 100:5.2 at pH = 3.24 underwent
multiple phase transitions upon heating, from a clear, free-flowing
liquid (<15 °C) to a clear, free-standing gel (15â46
°C) to a clear, free-flowing hot liquid (47â56 °C),
and a cloudy mixture (â„57 °C). With the increase of pH,
the sol-to-gel transition temperature (<i>T</i><sub>solâgel</sub>) shifted to higher values, while the gel-to-sol transition (<i>T</i><sub>gelâsol</sub>) and the clouding temperature
(<i>T</i><sub>clouding</sub>) of the sample remained essentially
the same. These transitions and the tunability of <i>T</i><sub>solâgel</sub> originated from the thermosensitive properties
of two blocks of the diblock copolymer and the pH dependence of the
LCST of PÂ(DEGEA-<i>co</i>-AA), which were confirmed by dynamic
light scattering and differential scanning calorimetry studies. Using
the vial inversion test method, we mapped out the C-shaped solâgel
phase diagrams of the diblock copolymer in aqueous buffers in the
moderate concentration range at three different pH values (3.24, 5.58,
and 5.82, all measured at âŒ0 °C). While the upper temperature
boundaries overlapped, the lower temperature boundary shifted upward
and the critical gelation concentration increased with the increase
of pH. The AA content in PTEGMA-<i>b</i>-PÂ(DEGEA-<i>co</i>-AA) was found to have a significant effect on the pH
dependence of <i>T</i><sub>solâgel</sub>. For PTEGMA-<i>b</i>-PÂ(DEGEA-<i>co</i>-AA) with a molar ratio of
DEGEA to AA units of 100:10, the <i>T</i><sub>solâgel</sub> of its 25 wt % aqueous solution increased faster with the increase
of pH than that of PTEGMA-<i>b</i>-PÂ(DEGEA-<i>co</i>-AA) with a DEGEA-to-AA molar ratio of 100:5.2
Agarose Hydrogels Embedded with pH-Responsive Diblock Copolymer Micelles for Triggered Release of Substances
Hybrid agarose hydrogels embedded
with pH-responsive diblock copolymers
micelles were developed to achieve functional hydrogels capable of
stimulus-triggered drug release. Specifically, a well-defined polyÂ(ethylene
oxide) (PEO)-based diblock copolymer, PEO-<i>b</i>-polyÂ(2-(<i>N</i>,<i>N</i>-diisopropylamino)Âethyl methacrylate)
(PEO<sub>113</sub>-<i>b</i>-PDPAEMA<sub>31</sub>, where
the subscripts represent the degrees of polymerization of two blocks),
was synthesized by atom transfer radical polymerization. PDPAEMA is
a pH-responsive polymer with a p<i>K</i><sub>a</sub> value
of 6.3. The PEO<sub>113</sub>-<i>b</i>-PDPAEMA<sub>31</sub> micelles were formed by a solvent-switching method, and their pH-dependent
dissociation behavior was investigated by dynamic light scattering
and fluorescence spectroscopy. Both studies indicated that the micelles
were completely disassembled at pH = 6.40. The biocompatibility of
PEO<sub>113</sub>-<i>b</i>-PDPAEMA<sub>31</sub> micelles
was demonstrated by <i>in vitro</i> primary cortical neural
culture. Hybrid agarose hydrogels were made by cooling 1.0 wt % agarose
solutions that contained various amounts of PEO<sub>113</sub>-<i>b</i>-PDPAEMA<sub>31</sub> micelles at either 2 or 4 °C.
Rheological measurements showed that the mechanical properties of
gels were not significantly adversely affected by the incorporation
of diblock copolymer micelles with a concentration as high as 5.0
mg/g. Using Nile Red as a model hydrophobic drug, its incorporation
into the core of diblock copolymer micelles was demonstrated. Characterized
by fluorescent spectroscopy, the release of Nile Red from the hybrid
hydrogel was shown to be controllable by pH due to the responsiveness
of the block copolymer micelles. Based on the prominent use of agarose
gels as scaffolds for cell transplantation for neural repair, the
hybrid hydrogels embedded with stimuli-responsive block copolymer
micelles could allow the controlled delivery of hydrophobic neuroprotective
agents to improve survival of transplanted cells in tune with signals
from the surrounding pathological environment