Lee Chin-Fen, Wang Mu-Rong, Lin Tsang-Lang, Yang Ching-Hsun, Chen Li-Jen
Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Department of Engineering and System Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
Langmuir. 2020 Aug 4;36(30):8929-8938. doi: 10.1021/acs.langmuir.0c01437. Epub 2020 Jul 24.
Understanding the dynamic behavior of hydrogel formation induced by a temperature ramp is essential for the design of gel-based injectable formulation as drug-delivery vehicles. In this study, the dynamic behavior of the hydrogel formation of Pluronic F108 aqueous solutions within different heating rates was explored in both macroscopic and microscopic views. It was discovered that when the heating rate is increased, the gelation temperature window (hard gel region) shrinks and the mechanical strength of the hydrogel decreases. A given system at different heating rates would lead to different crystalline structural evolutions. The time-resolved small-angle X-ray scattering (SAXS) experiments at a heating rate of 10 °C/min disclose that the crystalline structure of micelle packing in the hydrogel exhibits a series of transitions: hexagonal close-packed (HCP) to face-centered cubic (FCC) and body-centered cubic (BCC) structures coexisting and then to the BCC structure along with the increasing temperature. For the system at equilibrium, the BCC structure exclusively dominates the system. Furthermore, the addition of a hydrophobic model drug (ibuprofen) to the F108 aqueous solution promotes hard gel formation at even lower temperatures and concentrations of F108. The SAXS results for the system with ibuprofen at a heating rate of 10 °C/min demonstrate a mixture of FCC and BCC structures coexisting over the whole gelation window compared to the BCC structure that exclusively dominates the system at equilibrium. The addition of ibuprofen would alter the structural evolution to change the delivery path of the encapsulated drug, which is significantly related to the performance of drug release.
了解由温度梯度引发的水凝胶形成的动态行为对于设计基于凝胶的可注射制剂作为药物递送载体至关重要。在本研究中，从宏观和微观角度探讨了不同加热速率下泊洛沙姆F108水溶液水凝胶形成的动态行为。研究发现，当加热速率增加时，凝胶化温度窗口（硬凝胶区域）缩小，水凝胶的机械强度降低。不同加热速率下的给定体系会导致不同的晶体结构演变。在10℃/min加热速率下的时间分辨小角X射线散射（SAXS）实验表明，水凝胶中胶束堆积的晶体结构呈现一系列转变：从六方密堆积（HCP）到面心立方（FCC）和体心立方（BCC）结构共存，然后随着温度升高转变为BCC结构。对于处于平衡状态的体系，BCC结构完全主导该体系。此外，向F108水溶液中添加疏水性模型药物（布洛芬）可在更低的F108温度和浓度下促进硬凝胶形成。在10℃/min加热速率下含布洛芬体系的SAXS结果表明，与平衡时完全由BCC结构主导的体系相比，在整个凝胶化窗口内FCC和BCC结构共存。布洛芬的添加会改变结构演变，从而改变包封药物的释放途径，这与药物释放性能显著相关。
