Introduction
The eye is known as a complex organ, and it has distinctive anatomy and physiology. The anterior and posterior segments make up each half of the eye. The anterior segment of the eye comprises one-third, while the remaining portion is composed of the posterior segment. The anterior section is made up of the cornea, conjunctiva, aqueous humor, iris, ciliary body, and lens. Posterior segments comprise sclera, choroid, retinal pigment epithelium, neural retina, optic nerve, and vitreous humor. Vision-threatening diseases affect the anterior and posterior segments of the eye. The diseases that affect the anterior segment include:
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Glaucoma (damages of optic nerve).
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Allergic conjunctivitis (inflammation of the conjunctiva).
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Anterior uveitis (middle layer of the eye is affected).
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Cataract (clouding of the lens).
What Are Ophthalmic Drug Delivery Systems?
Ophthalmic drug delivery systems encompass a range of techniques and technologies designed to deliver therapeutic agents to the eye. The important goal is to ensure that the medication reaches its intended target in the eye, such as the cornea, conjunctiva, or retina, while minimizing systemic side effects. Traditional medication administration techniques for the eye, including eye drops, have drawbacks like limited drug bioavailability because of things like quick blinking, fast tear drainage, and inadequate corneal penetration. Moreover, patient compliance with prescribed eye drop regimens can be erratic, leading to inadequate treatment outcomes. Ophthalmic drug delivery systems aim to overcome these limitations by providing controlled, sustained, and targeted drug delivery.
What Are Conventional Ocular Drug Delivery Systems?
Topical drop installation is prolonged delivery of liquid into the body slowly, or drop by a drop in the precorneal pocket is the widely recommended route of drug administration. Due to blinking reflex, most of the topically administered dose is lost. Only 20 % of the instilled amount is retained in the precorneal pocket through this route. Passive diffusion across the cornea occurs because of the concentration of drugs available in the precorneal area. For efficient drug delivery systems with eye drops, high penetration of the cornea with longer drug cornea contact time is required. To improve the penetration of cornea iontophoresis (low amplitude electrical current is used to promote the migration of drug), prodrugs (a drug that is inactive and becomes active by metabolic or Physico-chemical transformation, ion-pair forming agents, and cyclodextrins are employed. Most of the prescriptions available in the market are topical drops (70 %), including conventional eye drops because of manufacturing in bulk, high patient acceptability, good efficacy, stability, and cost-effectiveness.
Topical Liquid or Solution Eye Drops:
Topical drop is a non-invasive mode of ocular drug administration. It is the most convenient, safe, and active method. To improve the drug contact time, permeation and ocular bioavailability additives may be added to the topical eye. It consists of viscosity enhancers, permeation enhancers, and cyclodextrins.
Viscosity enhancers improve bioavailability by enhancing formulation viscosity. Examples include hydroxy methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, and polyalcohol.
Permeation enhancers modify corneal integrity. Bile salts, surface active compounds, chelating agents, and preservatives were investigated as potential permeation enhancers. It improves drug bioavailability.
Emulsions:
An emulsion-based ocular drug delivery system provides an advantage that improves the solubility and bioavailability of drugs.There are two varieties of emulsions: water in oil (w/o) and oil in water (o/w). O/w emulsion is the industry standard and is favored over the w/o method for the administration of ophthalmic drugs. The causes include decreased ocular pain and irritation, as well as higher ocular tolerance of o/w emulsion. AzaSite is one type of non-medicated emulsion for eye lubrication, along with Restasis and Refresh Endura.
Suspensions:
Suspension is another form of the non-invasive ocular topical drop drug system. It is known as the dispersion of a finitely divided insoluble active pharmaceutical ingredient in an aqueous solvent and also consists of suspending and dispersing agent. Suspension particles improve the drug contact time and the drug's duration of action. The duration of the drug depends on the particle size. A larger particle size retains the drug for a more extended period, and the drug dissolution is less. Therefore, optimal particle size is essential to have optimum drug activity. TobraDex suspension is the most commonly used commercial product. TobraDex is a combined product of Tobramycin and Dexamethasone.
What Are Novel Ocular Drug Delivery Systems?
Nanotechnology-Based Ocular Drug Delivery:
Nanotechnology-based ophthalmic formulations are used for both anterior and posterior segment drug delivery. Systems based on nanotechnology that have the right particle size result in minimal discomfort, sufficient bioavailability, and compatibility with the ocular tissue. Several types have been developed for ocular drug delivery, such as nanoparticles, nanosuspensions, liposomes, nano micelles, and dendrimers. Many of them show good results and have enhanced bioavailability.
Nanomicelles:
Nanomicelles are clear aqueous solutions and are the most commonly used ones. The nanomicelles are made up of amphiphilic molecules (any compound that contains two distinct covalently bound components). These molecules act as a surfactant (a detergent that reduces surface tension) or polymeric. They are tiny, simple to prepare, highly capable of encapsulating drugs, and produce aqueous solutions thanks to their hydrophilic nanomicellar corona. The micellar formulation can increase the bioavailability of the drug in ocular tissues and enhance therapeutic outcomes.
Nanoparticles:
Lipids, proteins, and natural or artificial polymers such albumin, sodium alginate, chitosan, polylactic acid, and polycaprolactone make up nanoparticles. It is a colloidal carrier with a size range of 10 to 1000 nm. Nanoparticles can be nanocapsules or nanospheres.
In nanocapsules, the drug is within the polymeric shell, while in nanospheres the drug is uniformly distributed throughout the polymeric matrix. Nanoparticles show promising results for ocular drug delivery because of their small size and cause less irritation and sustained release property, avoiding frequent administration. In addition, nanoparticles are developed to improve precorneal residence time. Examples of strengthening precorneal residence time include polyethylene glycol chitosan and hyaluronic acid. Chitosan coating is positively charged, binds to the negatively charged corneal surface, improves precorneal residence, and decreases clearance.
Conclusion
The major challenge faced by an ophthalmologist is the ocular drug delivery system. Topical eye drops are the safest and quick method, especially for anterior segment diseases. However, various precorneal, dynamic and static visual barriers restrict the delivery of drugs. With advancing technology and research, many new drug delivery devices or techniques have developed that surpass these barriers and maintain an appropriate amount of drugs in the tissues. Conventional topical solutions are advancing with permeation and viscosity enhancers for anterior segment delivery. In addition, there is the development of suspensions, emulsions, and ointments. Various nanoformulations have also been developed for ocular drug delivery in the anterior segment.
