Modeling of hyperbranched polyesters as hosts for the multifunctional bioactive agent Shikonin

Area of Science:

• Polymer Chemistry
• Computational Chemistry
• Drug Delivery Systems

Background:

• Hyperbranched polyesters like Boltorn® are utilized in various applications.
• Understanding drug-polymer interactions is crucial for developing effective drug delivery systems.
• Shikonin is a bioactive agent with therapeutic potential.

Purpose of the Study:

• To investigate the non-covalent association mechanisms between Shikonin and hyperbranched polyesters.
• To explore the influence of polyester generation and concentration on Shikonin complexation.
• To elucidate the roles of hydrogen bonding and spatial constriction in the binding process.

Main Methods:

• Fully atomistic molecular dynamics simulations were performed.
• Simulations were conducted in ethanol solutions under excess drug conditions.
• Analysis included static and dynamic information to assess polymer/drug complexation.

Main Results:

• Two primary binding mechanisms were identified: hydrogen bonding and spatial constriction.
• Polyester size, structural flexibility, intrapolymer hydrogen bonding, and concentration were found to be critical factors.
• These parameters decisively affect the associative behavior of polyester/Shikonin complexes and drug molecule behavior in solution.

Conclusions:

• The study provides a detailed understanding of Shikonin-hyperbranched polyester interactions.
• Key factors influencing complexation efficacy and drug behavior in solution were elucidated.
• Findings can inform the design of more complex multi-polyester drug delivery systems.