Complex anatomy and physiology of the ocular system can be attributed to the fragility of human eyes as they are extension of the human brain outside the skull, which makes them the most vulnerable human body part. Several routes of drug administration are available, however, the ocular drug formulations most frequently administered for ocular pathologies (as topical instillation) are eye drops.
The intriguing anatomy and physiology that helps protect ocular structures hinder the absorption of topically instilled drugs as well.
Why is that so?
After a drug is administered as eye drops, it can be absorbed via two pathways. Either through the corneal route or non-corneal routes such as conjunctiva or sclera. Drug absorption through the corneal pathway is a struggle, the cornea has been designed to repel every foreign particle for which a well-fortified barrier is built. Conjunctiva being hydrophilic, is 15 times more permeable to drugs in comparison to the cornea. Scleral fibrils and perivascular spaces help a drug diffuse through the sclera.
Several other barriers also hinder drug absorption reducing drugs bioavailability when given as topical instillation like tears dilution and per corneal fluid drainage in nasolacrimal duct leading to systemic absorption and wastage of drug, blinking, corneal epithelial membrane's low permeability, stroma and blood-aqueous barrier, conjunctival blood flow, and lymph flow.
All of these factors result in the need for frequent instillation of drugs.
Recent advances in medical science have developed innovative ways to increase the bioavailability of eye drops. These could be sub-micron to macro size:
●Prodrugs: Addition of hydroxyl or carboxyl groups, so that these produce more lipophilic ester prodrugs which are absorbed more easily into the cornea.
●Enhancers: these increase the permeability of drugs through ocular membranes as an example chelating agents and bile salts.
●Mucus penetrating particles: these are nano-sized particles not caught in mucus mesh.
●Therapeutic contact lenses: these are used for the treatment of corneal ulcers, to relieve pain in the eye and more.
●Collagen corneal shields: it is a lens made from natural protein, it is used as lubricant in eyes instead of artificial tears.
Several other methods like nanogels, liposomes, microemulsions, lipid, and polymeric nanoparticles, cyclodextrins, dendrimers, and nanocrystals are also available. Understanding the drug delivery routes while keeping in view the ocular anatomy can help us in the effective delivery of drugs specifically for anterior segment pathologies.
A wide variety of medications is available for ocular pathologies through several routes of administration as an example local application like ointments, eye drops as local instillation, injections like peribulbar, retrobulbar, intracameral or intravitreal, and systemic administration by oral drugs. Which route is best for what pathology is dictated by the route of administration is most effective, well tolerated, least toxic in the right amount, achieves maximum effect and compliance.