Phosphorylated silk fibroin matrix for methotrexate release.

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Materials Chemistry

Background:

• Silk fibroin is a promising biomaterial for drug delivery applications.
• Understanding interactions between silk fibroin and drugs is crucial for optimizing delivery systems.
• Methotrexate (MTX) is a model anticancer drug used to evaluate drug-eluting matrices.

Purpose of the Study:

• To investigate the interactions between silk fibroin and methotrexate (MTX) in a drug delivery matrix.
• To determine whether electrostatic or structural factors dominate the interaction and influence MTX release.
• To explore the effect of matrix preparation conditions (pH, phosphorylation) on MTX release profiles.

Main Methods:

• Silk fibroin films were prepared by casting at different pH values (7.2 and 3.5).
• Phosphorylated silk fibroin was synthesized using Protein Kinase A and incorporated at controlled ratios.
• In vitro release studies were conducted, assessing MTX release under various conditions (proteolytic enzymes, pH changes).

Main Results:

• In vitro release data indicated that structural interactions, rather than electrostatic ones, primarily govern the relationship between silk fibroin and MTX.
• MTX release was enhanced by proteolytic enzymes and higher pH conditions.
• Acidified silk fibroin matrices (pH 3.5), exhibiting higher beta-sheet content and crystallinity, showed reduced MTX retention.

Conclusions:

• Structural interactions significantly outweigh electrostatic forces in the silk fibroin-methotrexate system.
• Matrix structural integrity and composition are key determinants of drug release kinetics.
• The findings provide insights for designing silk-based drug delivery systems with tailored release characteristics.