Drug reservoirs in topical therapy

Area of Science:

• Ophthalmology
• Pharmacology
• Drug Delivery

Background:

• The cornea serves as a primary barrier to ocular drug penetration.
• Understanding drug distribution within corneal layers is crucial for effective topical ophthalmic therapies.

Purpose of the Study:

• To investigate the nictitating membrane, corneal epithelium, and corneal stroma as potential drug reservoirs.
• To compare the distribution of hydrophilic (epinephrine) and lipophilic (chloramphenicol) drugs within corneal tissues.

Main Methods:

• Topical application of radiolabeled D,L-epinephrine HCl (hydrophilic) and chloramphenicol (lipophilic) to rabbit eyes.
• Assay of drug and metabolite levels in corneal tissues (epithelium, stroma-endothelium) and aqueous humor up to 24 hours post-application.
• Evaluation of the effect of the nictitating membrane on drug distribution.

Main Results:

• Corneal stroma-endothelium showed similar or higher concentrations of epinephrine and its metabolites compared to the epithelium, on a per-mg basis.
• Chloramphenicol concentrations were higher in the corneal epithelium than in the stroma-endothelium within the first 130 minutes.
• Despite regional concentration differences, the larger mass of the corneal stroma-endothelium made it the primary drug reservoir overall.
• The nictitating membrane had minimal impact on drug levels in corneal tissues or aqueous humor.

Conclusions:

• The corneal stroma-endothelium is the major drug reservoir due to its greater tissue mass, influencing overall drug availability.
• Drug physicochemical properties dictate initial distribution between corneal epithelium and stroma-endothelium.
• Topical ocular drug distribution is complex and influenced by tissue composition and drug characteristics.