Dual pH-Responsive Hydrogel Actuator for Lipophilic Drug Delivery

Abstract

As one of the most promising drug delivery carriers, hydrogels have received considerable attention in recent years. Many previous efforts have focused on diffusion-controlled release, which allows hydrogels to load and release drugs in vitro and/or in vivo. However, it hardly applies to lipophilic drug delivery due to their poor compatibility with hydrogels. Herein, we propose a novel method for lipophilic drug release based on a dual pH-responsive hydrogel actuator. Specifically, the drug is encapsulated and can be released by a dual pH-controlled capsule switch. Inspired by the deformation mechanism of Drosera leaves, we fabricate the capsule switch with a double-layer structure that is made of two kinds of pH-responsive hydrogels. Two layers are covalently bonded together through silane coupling agents. They can bend collaboratively in a basic or acidic environment to achieve the “turn on” motion of the capsule switch. By incorporating an array of parallel elastomer stripes on one side of the hydrogel bilayer, various motions (e.g., bending, twisting, and rolling) of the hydrogel bilayer actuator were achieved. We conducted an in vitro lipophilic drug release test. The feasibility of this new drug release method is verified. We believe this dual pH-responsive actuator-controlled drug release method may shed light on the possibilities of various drug delivery systems.

Engineering bioactive synthetic polymers for biomedical applications: a review with emphasis on tissue engineering and controlled release

“…Actuation, or the ability of a material to move or change its shape in response to a stimulus, is a functionality that is being pursued by tissue engineers for diverse applications including controlled release of cargos (e.g., nucleic acids, drugs, growth factors, and other proteins), development of soft robots with potential applications in biomedicine, and fabrication of dynamic ''smart'' scaffolds for tissue engineering applications. [258][259][260] All these devices/applications must often be coupled with sensing capabilities. 261,262 Programmable actuation behaviours can be useful for overcoming the various challenges and limitations of biomedical devices; for instance, actuation may enable a fine control of biological events by adding a fourth dimension to the biological system (i.e., the temporal coordinate).…”

“…For this reason, chemically responsive actuators are a more appealing option for tissue engineering applications. 258,[295][296][297][298][299][300][301] Chemically responsive bioactuators often respond to ionic strength charges or pH changes. The basic understanding of polymer-polymer, polymer-solvent, and polymer-solute interactions may lead to the engineering of SyPs-based actuators that undergo mechanical and shape transformations after responding to various external stimuli.…”

“…Han et al developed pH responsive valves that enabled precise control of the opening and closing of drug delivery systems. 258 These valves were made from polyacrylic acid (PAAc) and PAAm. The swelling ratio between PAAc and PAAm exhibits a dramatic shift around pH 6, and PAAm absorbs more water than PAAc below the threshold of 6.0.…”

“…(c) Precise shape/swelling control in polyacrylamide (PAAm) hydrogel actuators using DNA hairpin engineering (Cangialosi et al293 ). (d) pH-responsive valve made from polyacrylic acid (PAAc) and PAAm for a drug-delivery device (adapted from Han et al258 ). Scale bar: 2 mm.…”

Molecular Architectonics‐guided Design of Biomaterials

“…While hydrogels play a pivotal role in drug delivery, they are generally considered incompatible for lipophilic drugs. Shaoxing and coworkers developed dual pH‐responsive hydrogel actuators that can encapsulate and release the lipophilic drug when subjected to acidic and basic environments [93] . Polyampholytes with cationic and anionic moieties have the ability to mimic protein (synthetic or artificial chaperones) that help in modulating the protein misfolding and aggregation to treat proteinopathies like Alzheimer's disease.…”