RESUMEN
Hydrogels are promising ultrasound-responsive drug delivery systems. In this study, we investigated how different ultrasound parameters affected drug release and structural integrity of self-healing hydrogels composed of alginate or poloxamers. The effects of amplitude and duty cycle at low frequency (24 kHz) ultrasound stimulation were first investigated using alginate hydrogels at 2% w/v and 2.5% w/v. Increasing ultrasound amplitude increased drug release from these gels, although high amplitudes caused large variations in release and damaged the gel structure. Increasing duty cycle also increased drug release, although a threshold was observed with the lower pulsed 50% duty cycle achieving similar levels of drug release to a continuous 100% duty cycle. Poloxamer-based hydrogels were also responsive to the optimised parameters at low frequency (24 kHz, 20% amplitude, 50% duty cycle for 30 s) and showed similar drug release results to a 2.5% w/v alginate hydrogel. Weight loss studies demonstrated that the 2% w/v alginate hydrogel underwent significant erosion following ultrasound application, whereas the 2.5% w/v alginate and the poloxamer gels were unaffected by application of the same parameters (24 kHz, 20% amplitude, 50% duty cycle for 30 s). The rheological properties of the hydrogels were also unaffected and the FTIR spectra remained unchanged after low frequency ultrasound stimulation (24 kHz, 20% amplitude, 50% duty cycle for 30 s). Finally, high-frequency ultrasound stimulation (1 MHz, 3 W.cm-2, 50% duty cycle) was also trialled; the alginate gels were less responsive to this frequency, while no statistically significant impact on drug release was observed from the poloxamer gels. This study demonstrates the importance of ultrasound parameters and polymer selection in designing ultrasound-responsive hydrogels.