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.
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