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Intraocular Barriers in Drug Delivery

  • 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.


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