Stochastic Lattice-Based Modeling of Macromolecule Release from Degradable Hydrogel

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Computational Modeling

Background:

• Degradable hydrogels are promising for controlled drug delivery.
• Understanding drug release mechanisms from these matrices is crucial for therapeutic efficacy.
• Existing models often simplify the complex, time-dependent nature of hydrogel degradation.

Purpose of the Study:

• To develop a 3D lattice-based computational model for simulating macromolecular drug release from degradable hydrogels.
• To incorporate degradation-induced network heterogeneity and varying diffusion coefficients.
• To validate the model against experimental data and investigate the interplay of network properties and release kinetics.

Main Methods:

• Developed a 3D lattice model incorporating varying diffusion coefficients based on an exponential node-diffusivity relationship.
• Modeled increasing diffusivity over time due to crosslink node degradation.
• Introduced a scaling ratio derived from the random walk equation to manage computational size and enable comparison with experimental data.
• Utilized chemically crosslinked dextran hydrogels for experimental validation.

Main Results:

• The model successfully described experimental drug release data from dextran hydrogels.
• Demonstrated that degradation-induced network heterogeneity significantly influences drug release profiles.
• Showed that the initial hydrogel network structure and the hydrolysis rate of crosslink nodes are interdependent factors affecting drug release and cannot be analyzed in isolation.

Conclusions:

• The developed 3D lattice model provides a robust framework for simulating drug release from degradable hydrogels, accounting for network evolution.
• The study highlights the critical, inseparable roles of initial network architecture and crosslinking chemistry in determining drug release kinetics.
• This model can aid in the rational design of hydrogel-based drug delivery systems with predictable release profiles.