Model of transient drug diffusion across cornea

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Biomedical Engineering

Background:

• Topical drug delivery to the anterior eye segment is challenging due to biological barriers.
• Predicting drug bioavailability is crucial for effective ocular therapeutics.

Purpose of the Study:

• To develop and validate a mathematical model for predicting solute diffusion and bioavailability in the anterior chamber of the eye.
• To identify key physicochemical and physiological parameters influencing ocular drug delivery.

Main Methods:

• Development of a mathematical model simulating solute transient diffusion across the cornea.
• Inclusion of parameters such as solute molecular radius, octanol-to-water distribution coefficient (Phi), ocular membrane properties, tear fluid dynamics, and anterior chamber distribution volume (Vd) and clearance rate (Cla).

Main Results:

• Solute lipophilicity (Phi) is the primary determinant of drug bioavailability.
• Predicted bioavailability is 1-5% for lipophilic molecules (Phi>1) and <0.5% for hydrophilic molecules (Phi<0.01).
• Optimal bioavailability is predicted for solutes with a Phi of approximately 10. Maximum concentration (Cmax) and time to Cmax depend significantly on Phi, Vd, and Cla.

Conclusions:

• The developed model accurately predicts drug transport kinetics and bioavailability for topical ocular delivery.
• Strategies like reducing conjunctival-to-corneal permeability and precorneal drainage can enhance bioavailability.
• The model serves as a valuable tool for designing new ocular drug delivery systems and evaluating drug delivery in diseased eyes.