Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing.

Area of Science:

• Pharmacology and Pharmaceutical Sciences
• Medicinal Chemistry
• Biomaterials Science

Background:

• Coumarins possess diverse pharmacotherapeutic properties but suffer from poor aqueous solubility.
• Cyclodextrins (CDs) are widely used to improve the bioavailability of poorly soluble drugs.
• Complexation with cyclodextrins is a strategy to enhance coumarin's therapeutic applications.

Purpose of the Study:

• To investigate the formation and properties of coumarin-β-cyclodextrin inclusion complexes.
• To evaluate the effect of these complexes on drug solubility and stability.
• To assess the wound healing potential and anti-inflammatory mechanisms of coumarin-β-CD complexes.

Main Methods:

• Synthesis and characterization of 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC) inclusion complexes with β-cyclodextrin (β-CD) using lyophilization (FL) and mechanical mixture (MM) methods.
• Solubility, stability, and structural analysis of the inclusion complexes.
• In vivo wound healing studies in mice.
• Protein binding assays to investigate anti-inflammatory mechanisms.

Main Results:

• Inclusion complex formation significantly improved the aqueous solubility of DMC and MMC.
• The optimal molar ratio for stable complex formation was 2:1 coumarin/β-CD, stabilized by hydrogen bonds and π-π stacking.
• (DMC)2@β-CD (FL) and (MMC)2@β-CD (FL) demonstrated accelerated wound re-epithelialization, enhanced collagen deposition, and reduced inflammation markers in vivo.
• Protein binding studies suggested potential MEK inhibition as an anti-inflammatory mechanism.

Conclusions:

• Coumarin-β-CD inclusion complexes effectively enhance coumarin solubility and bioavailability.
• The lyophilized complexes exhibit significant potential for wound repair applications.
• These findings suggest the development of novel MEK inhibitors for anti-inflammatory therapies based on coumarin derivatives.