Intraocular barriers are structural and functional mechanisms that protect the eye while presenting significant challenges to drug delivery.
These barriers are categorized into static and dynamic barriers.
Intraocular Barriers in Drug Delivery
Static Barriers
These are anatomical structures that restrict drug penetration and distribution within the eye.
Cornea
Structure: Three layers – epithelium, stroma, and endothelium.
Barrier Characteristics:
Epithelium: Lipophilic layer, limits penetration of hydrophilic drugs.
Stroma: Hydrophilic layer resists lipophilic drugs.
Endothelium: Provides additional barrier function but is less restrictive than the epithelium.
Blood-Aqueous Barrier
Location: Formed by the tight junctions in non-pigmented epithelium of the ciliary body and non-fenestrated capillaries.
Function: Limits the movement of drugs from the bloodstream into the aqueous humor.
Blood-Retinal Barrier (BRB)
Components:
Inner BRB: Tight junctions between retinal capillary endothelial cells restrict large molecules and neurotoxins.
Outer BRB: Retinal pigment epithelial (RPE) cells regulate transport between the choroid and retina.
Role: Maintains retinal homeostasis, making drug delivery to the retina highly challenging.
Dynamic Barriers
These are physiological processes that influence drug clearance and absorption.
Tear Turnover and Drainage
Mechanism: Constant tear flow and reflex tearing dilute and wash away topically applied drugs.
Impact: Reduces the residence time of drugs on the ocular surface.
Conjunctival Absorption
Mechanism: Drugs absorbed into systemic circulation via conjunctival blood vessels.
Impact: Decreases the availability of the drug for ocular action, reducing efficacy.
Metabolic Enzymes
Location: Found in the cornea and other ocular tissues.
Function: Degrades drugs enzymatically, reducing their bioavailability and effectiveness.