In silico development of an inflammation-triggered β-cyclodextrin carrier for a redox-active vanadium-INAP-tryptophan...

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Inflammation-driven diseases involve localized oxidative stress and acidosis, limiting conventional anti-inflammatory drug efficacy.
• Poor site selectivity and systemic exposure hinder current therapeutic approaches.

Purpose of the Study:

• To computationally investigate an inflammation-responsive drug delivery system using beta-cyclodextrin (β-CD) encapsulation of a vanadium complex.
• To explore selective destabilization within pathological microenvironments for targeted drug release.

Main Methods:

• In silico investigation of β-CD encapsulation of VO-INAP-tryptophan.
• Simulation of inflammatory conditions (acidic pH, high dielectric constant, elevated temperature).
• Frontier molecular orbital analysis and global reactivity descriptors to assess stability and reactivity.

Main Results:

• Identified a specific inclusion conformation susceptible to solvent competition and electronic destabilization for selective release.
• Computational model demonstrated selective destabilization under simulated inflammatory conditions.
• Component-resolved electronic analysis revealed synergistic roles of vanadium and tryptophan in redox activity.

Conclusions:

• The study provides computational insights for designing inflammation-responsive supramolecular delivery systems.
• Beta-cyclodextrin (β-CD) architectures show potential for optimizing redox-active metal complex therapies.
• Further experimental validation is needed to confirm the therapeutic potential.