Structural reinforcement of Pluronic F127/chitosan thermoresponsive hydrogels through polydopamine incorporation for controllable drug transport.
TL;DR
Results establish PDA-mediated non-covalent reinforcement as an effective crosslinker-free strategy for engineering thermoresponsive hydrogels with tunable network mechanics and controllable NIR-responsive drug transport for localized chemo-photothermal therapy.
Abstract
Thermoresponsive Pluronic-based hydrogels are promising injectable drug delivery platforms but are often limited by weak mechanical integrity and control over drug transport. In this study, we report a polydopamine (PDA)-reinforced Pluronic F127/chitosan composite hydrogel, PCP-DOX, designed to strengthen network integrity and enable near-infrared (NIR)-responsive release without chemical crosslinkers. We have characterized the composite hydrogel for microstructure, rheology, and release kinetics, with photothermal performance and in vitro therapeutic efficacy evaluated under 808 nm NIR irradiation. We found a progressive network densification observed by electron microscopy together with a threefold increase in elastic modulus from approximately 11 kPa to 29 kPa. PCP-DOX exhibited a DOX entrapment efficiency of 98.24 ± 0.20%, indicating effective drug retention. Cumulative doxorubicin (DOX) release at 72 h decreased from 85.5% to 73.3% in the composite relative to the Pluronic-only system. Korsmeyer-Peppas modeling provided the best fit for the release kinetics, suggesting Fickian diffusion-governed transport, with the diffusion exponent increasing from 0.2975 to 0.4531 in the composite system, indicating enhanced diffusional resistance within the network. NIR irradiation at 1.0 W/cm2 enabled transient photothermal modulation of the composite network, producing stepwise release enhancement across repeated irradiation cycles. In vitro studies confirmed cytocompatibility of the blank hydrogel carrier, and combined NIR and DOX treatment yielded greater cytotoxicity than either modality alone, where the predominant cell death mechanism was determined to be apoptosis. These results establish PDA-mediated non-covalent reinforcement as an effective crosslinker-free strategy for engineering thermoresponsive hydrogels with tunable network mechanics and controllable NIR-responsive drug transport for localized chemo-photothermal therapy.