Bidirectional thermo-switch hydrogels with size-selective diffusion for programmable delivery of medicines

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Precise control over molecular transport is crucial for effective stimulus-responsive drug delivery.
• Existing systems often lack the ability to modulate transport in opposite directions based on physiological cues.

Purpose of the Study:

• To develop a novel hydrogel system capable of bidirectional, temperature-dependent drug release.
• To investigate the potential of this system for co-delivery of macromolecular and small-molecule therapeutics.

Main Methods:

• Fabrication of Bidirectional Thermo-Switch (BiTS) hydrogels using poly(N-isopropylacrylamide) (pNIPAam) with integrated ionic domains.
• Characterization of hydrogel network structure, thermal transitions, and swelling behavior.
• In vitro and ex vivo drug release studies using cyclosporine A (CsA) and ketoprofen (Keto) under thermal cycling.

Main Results:

• BiTS hydrogels exhibit tunable thermal transitions near physiological temperatures.
• Cooling promotes mesh expansion and enhanced release of CsA, while heating contracts the network, suppressing CsA release and accelerating Keto release.
• Demonstrated reversible, repeatable bidirectional transport and successful co-delivery of therapeutics ex vivo with maintained cytocompatibility.

Conclusions:

• The BiTS hydrogel platform enables temperature-dependent inversion of molecular transport within a single matrix.
• This system represents a promising thermo-responsive dual-regime drug delivery strategy with potential therapeutic applications.