Modeling of drug release from collagen matrices

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Physics

Background:

• Drug release from collagen matrices is typically diffusion-controlled but influenced by degradation and drug-matrix interactions.
• Crosslinking insoluble collagen matrices reduces water uptake and prolongs drug release.
• Existing models often do not fully capture the complex dynamics of swelling and release.

Purpose of the Study:

• To develop and validate a one-dimensional model for describing water penetration, swelling, and drug release from crosslinked collagen matrices.
• To incorporate mechanisms like Fickian diffusion, swelling-induced convection, and matrix crosslinking effects.
• To provide a predictive tool for optimizing drug release profiles from collagen-based delivery systems.

Main Methods:

• A one-dimensional model was developed based on Fickian diffusion and a volume balance for swelling.
• A moving boundary approach was used to account for the phase separation in thermally crosslinked matrices.
• Biquadratic finite elements in space and time were employed to solve the governing equations, with a closed-form solution derived for constant diffusion coefficients.

Main Results:

• The model accurately describes water penetration, swelling, and drug release kinetics in insoluble collagen matrices.
• The numerical method demonstrated stability and high accuracy, even with initial time singularities.
• Model predictions were verified against experimental data for matrices with varying degrees of chemical and thermal crosslinking.

Conclusions:

• The developed model provides a robust framework for understanding and predicting drug release from crosslinked collagen matrices.
• The incorporation of swelling dynamics and crosslinking significantly improves the accuracy of release profile predictions.
• This work contributes to the rational design of advanced collagen-based drug delivery systems with tailored release characteristics.