Intracorneal melatonin delivery using 2-hydroxypropyl-β-cyclodextrin ophthalmic solution for granular corneal...

Area of Science:

• Ophthalmology
• Materials Science
• Pharmacology

Background:

• Melatonin (MT) is an antioxidant with potential for treating granular corneal dystrophy type 2 (GCD2).
• Current MT formulations may have limited solubility, stability, and ocular absorption, and can cause eye irritation.
• Cyclodextrins (CDs) are known excipients for improving drug delivery.

Purpose of the Study:

• To develop and characterize melatonin-cyclodextrin complexes for improved ophthalmic delivery.
• To evaluate the solubility, stability, ocular absorption, and irritation potential of MT/CD formulations.
• To assess the therapeutic efficacy of MT/HPβCD eye drops for GCD2 treatment.

Main Methods:

• Formation and characterization of MT complexes with αCD, βCD, γCD, and 2-hydroxypropyl-βCD (HPβCD) using phase solubility studies.
• Evaluation of ocular irritation in rabbit models.
• Quantification of MT concentration in corneal tissues (epithelium, stroma, endothelium) after topical administration.
• Assessment of formulation stability over 60 days.

Main Results:

• Phase solubility studies indicated Higuchi's A_L-type profiles for all MT/CD complexes.
• The MT/HPβCD complex exhibited the highest MT solubility (2.75 mg/mL).
• HPβCD inclusion significantly reduced eye irritation compared to MT alone.
• Elevated MT concentrations were observed in all corneal layers following administration of MT/HPβCD formulations.
• Formulations demonstrated good stability over 60 days with no significant changes in pH, osmolarity, or MT content.

Conclusions:

• MT/HPβCD formulations offer a promising approach for enhanced ocular delivery of melatonin.
• These formulations can effectively reduce eye irritation and improve MT stability.
• The developed MT/HPβCD eye drops show potential for improved therapeutic efficacy in GCD2 treatment.