Temperature-Dependent Self-assembly and Dynamic Effect of Hydrogel Formation for Binary Amphiphilic Copolymer System

• Main Authors: Chin-Fen Lee, 李沁芬
• Other Authors: 陳立仁
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/fnjer3

博士 === 國立臺灣大學 === 化學工程學研究所 === 107 === Pluronic, a series of amphiphilic and biodegradable tri-block copolymers, has been widely applied on industry and biomedical science. Fundamental properties of Pluronics and its potential applicability has been kindly realized. However, there often remains unpredictable situations when applying it onto clinical treatment. Hence, we proceeded a series of studies starting from co-micellization between binary Pluronic copolymers to investigate molecular interactions. Then, the studies were extended to hydrogel formed by the stackings of micelles in concentrated solution. It allows us understand the unpredictable phase changes while applying it onto organisms. Firstly, we established two different perspectives to systematically vary the resemblance between parent copolymers establishing 7 systems: different block chain length at same hydrophilicity (Fx8 = F108, +F98, +F88, and +F68), as well as various hydrophobicities at same moiety of hydrophobic chain (F8x = F88, +F87, and +P84). Seven Pluronics with consecutively different properties were blend with Pluronic L92 to discuss how lamellar aggregates (L92) interact with the molecules which self-assemble into spherical micelles. We discovered that copolymers with longer hydrophobic chain are more capable of breaking down large aggregates into mixed micelles. However, parent copolymers with distinct hydrophobic chain lenghs do not affirmatively lead to non-cooperative binding, such as the system L92 + P84. Successively, Pluronic L92 was substituted by P123 to study co-micellization behaviors in the systems containing only micelles. It was evidenced that micelles are mainly formed by the copolymer (P123) with a lower critical micelle temperature (CMT) initially. Raising temperature dehydrates the other Pluronic with a higher CMT to be integrated into the neat P123 micelles developing mixed micelles. Through the small angle x-ray scattering (SAXS) experiment, mixed micelle is consisted of a core and two shells in which thickness of the first and total shell is equal to that of P123 and F8x or Fx8, respectively. SAXS results also demonstrate that hydrophobic drug - ibuprofen is mainly encapsulated in the core of neat micelles developed at low temperatures. Moreover, we discovered that mixed systems with P84 exhibits the most outstanding solubilization capacity to ibuprofen with its smallest and most stable aggregate (or micelle) sizes. Raising concentration or temperature of the system promotes the hydrophobic effect and triggers stackings of micelles into hard gel. We focused on the temperature induced changes of gel formation using Pluronic F108, F108 + P103 (2/1 wt%) and F108 + P123 (2/1 and 1/1 wt%). We discovered that molecule motions at heating rate below 0.1 °C/min approaches equilibrium phase changes of gelation process. Furthermore, gelation window (hard gel region) becomes smaller as heating rate gets faster. Moreover, different heating rates lead to microstructural changes of crystalline phases at different temperatures according to the time-resolved SAXS experiments. As heating rate increases (10 °C /min), the possibility of appearance of hexagonal close packing (HCP) and face centered cubic structure (FCC) structures increases. While heating rate decreases (0.1 °C /min), body centered cubic structure (BCC) phases dominate the system from lower temperatures. Also, incorporating ibuprofen into the system promotes hydrogel formation, but decreases the domain of ordered structures. Furthermore, we found that micelles with uniform and long corona chains exhibit higher capacity to tether other micelles. Interestingly, despite weaker stiffness of the hard gel, mixed micelles with non-uniform corona chains promote gel formation at low temperature.