Ultrasound-responsive hyaluronic acid hydrogel of hydrocortisone to treat osteoarthritis.

One of the practical ways to manage the disease flares of arthritis is using an intra-articular depot formulation of glucocorticoids. Hydrogels, as controllable drug delivery systems, are hydrophilic polymers with distinctive properties, such as remarkable water capacity and biocompatibility. This study aimed to design an injectable thermo-ultrasound-triggered drug carrier based on Pluronic® F-127, hyaluronic acid, and gelatin. The in situ hydrogel loaded by hydrocortison was developed and D-optimal design was used to formulate the process. The optimized hydrogel was combined with four different surfactants to better regulate the release rate. In situ gels composed of the hydrocortisone-loaded hydrogel and hydrocortisone-loaded mixed-micelle hydrogel were characterized. The hydrocortisone-loaded hydrogel and selected hydrocortisone-loaded mixed-micelle hydrogel showed a spherical shape and were nano-sized with a unique thermo-responsive nature able to prolong drug release. The ultrasound-triggered release study showed that drug release was time-dependent. By inducing osteoarthritis in a rat model, behavioral tests and histopathological analyses were carried out on the hydrocortisone-loaded hydrogel and a particular hydrocortisone-loaded mixed-micelle hydrogel. In vivo results showed that the selected hydrocortisone-loaded mixed-micelle hydrogel improved the status of the disease. Results highlighted the potential of ultrasound-responsive in situ-forming hydrogels as hopeful formulas for efficient treatment of arthritis.