Microgels as drug carriers for sonopharmacology

Abstract

The ultrasound‐induced cleavage of covalent and non‐covalent bonds to activate drugs (sonopharmacology) is a promising concept to gain control over the action of active pharmaceutical ingredients by an external trigger. Previously, linear polymer architectures bearing drug payloads were exploited for drug release by using the principles of polymer mechanochemistry. In this work, the carrier design is altered by the polymer topology to improve the ultrasound‐triggered release of covalently anchored drugs from polymer scaffolds. We use microgels crosslinked by mechanoresponsive disulfides and copolymerized with Diels‐Alder adducts of furylated payload molecules and acetylenedicarboxylate. Force‐induced thiol formation induces a Michael‐type addition liberating the payload from the microgels. The use of microgels significantly reduces sonication times compared to linear polymer chains and shields the cargo efficiently from non‐triggered activation using ultrasound that produces inertial cavitation at a frequency of 20 kHz as model condition.

Microgels react to force: mechanical properties, syntheses, and force-activated functions

“…Recently, covalently connected mechanophores have also been used to develop a mechanoresponsive carrier system for the release of cargo molecules from microgels. 137 The mechanophores have been incorporated alongside latent drugs into linear copolymers, which then formed microgels upon crosslinking with mechanoresponsive disulfides. It has been shown that the ultrasound-induced disulfide scission generates free thiols in the system initiating an intramolecular release cascade reaction.…”

Mechanochemistry of dynamic chalcogen-containing polymers: a minireview

“…To solve this problem, microgels were investigated as drug carriers instead of linear polymers. 74 Microgels are colloidally dissolved networks with a size of several hundred nanometres, and have been reported to be extremely sensitive to external force stimuli. 75 Perhaps due to their bulkier sizes compared with polymer chains in solutions, stimuli like sonication could generate greater forces in microgels.…”

Force ahead: Emerging Applications and Opportunities of Polymer Mechanochemistry

“…On the other hand, mechanophores were incorporated into polymer structures for which the topology drastically increased the mechanochemical reactivity and thereby decreased the necessary ultrasound doses. For example, this was achieved by designing mechanochemically responsive ultrahigh molar mass polyaptamers as supramolecular groups to inhibit the activity of bioactives, , gold nanoparticle assemblies, , genetically engineered proteins, microgels, and polymer brushes . Consequently, sonication times using a classical immersion probe sonicator at 20 kHz could be reduced by 1–2 orders of magnitude, i.e., from hours to seconds.…”