Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Computational Modeling

Background:

• Protease dysregulation is implicated in diseases like chronic wounds.
• Current drug delivery methods often lack precise control over therapeutic activity.
• Hydrogel-based systems offer potential for localized and responsive drug release.

Purpose of the Study:

• To engineer a biocompatible hydrogel drug delivery platform for protease inhibition.
• To achieve homeostasis of protease activity using a closed-loop feedback control system.
• To investigate the platform's performance using in silico finite element modeling.

Main Methods:

• Developed a hydrogel matrix with covalently tethered peptide-drug conjugates.
• Utilized finite element modeling (FEM) to simulate drug release kinetics and enzyme-drug interactions.
• Investigated the release of a matrix metalloproteinase-9 (MMP9) inhibitor (MAG283).

Main Results:

• FEM simulations accurately modeled transport-limited drug release, considering enzyme diffusion and kinetics.
• The platform demonstrated potential for targeted homeostasis of MMP9 activity.
• Key engineering parameters identified as hydrogel microsphere radii and peptide-inhibitor conjugate concentration.

Conclusions:

• The engineered hydrogel platform shows promise for homeostatic drug delivery.
• Closed-loop feedback control offers a new paradigm for managing biochemical pathway activity.
• Further realization of this approach could significantly advance therapeutic strategies for protease-mediated diseases.