Ultrasound-Induced Drug Release from Stimuli-Responsive Hydrogels

Abstract

Stimuli-responsive hydrogel drug delivery systems are designed to release a payload when prompted by an external stimulus. These platforms have become prominent in the field of drug delivery due to their ability to provide spatial and temporal control for drug release. Among the different external triggers that have been used, ultrasound possesses several advantages: it is non-invasive, has deep tissue penetration, and can safely transmit acoustic energy to a localized area. This review summarizes the current state of understanding about ultrasound-responsive hydrogels used for drug delivery. The mechanisms of inducing payload release and activation using ultrasound are examined, along with the latest innovative formulations and hydrogel design strategies. We also report on the most recent applications leveraging ultrasound activation for both cancer treatment and tissue engineering. Finally, the future perspectives offered by ultrasound-sensitive hydrogels are discussed.

Keywords: Tissue engineering; cancer therapy; controlled drug release; drug delivery; hydrogels; polymers; smart hydrogels; stimuli-responsive; thermoresponsive materials; ultrasound.

Figure 1

Ultrasound-sensitive hydrogels are designed to respond to ultrasound (either low or high-intensity) via thermal or non-thermal effects. Applications for these drug delivery systems include cancer therapy and tissue engineering.

Figure 2

Mechanisms of the ultrasound response of hydrogels. Acoustic energy can be transferred either via thermal or mechanical effects.

Figure 3

Overview of parameters influencing the design of ultrasound-responsive polymer-based hydrogels.

Figure 4

Design of ultrasound-responsive supramolecular PEG hydrogels crosslinked with a host-guest interaction between PEG-β-cyclodextrin and PEG-adamantane. This hydrogel matrix was developed by Yamaguchi et al. [100] and used for the controlled delivery of protein payloads.

Figure 5

Design of ultrasound-responsive mechanophores embedded into PEG hydrogels, generating reactive oxygen species (ROS) when activated by high-intensity focused ultrasound. This hydrogel matrix was developed by Kim et al. [134] and used for the selective elimination of cancer cells in vitro.