Recent Advances in Ophthalmic Drug Delivery

Abstract

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert ™ (~6 months), Retisert ™ (~3 years) and Iluvien ™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems.The current ophthalmology market is primarily driven by age-and lifestyle-related diseases, such as macular degeneration, cataracts, diabetic retinopathy and glaucoma. Dry eye syndrome, inflammation and ocular allergies are also contributing significantly. Traditionally, antiglaucoma products held the major market share. Driven by demographic trends such as an increase in aged population and lifestyle factors, the overall market for ophthalmic therapeutics is expected to undergo considerable and consistent growth during the next decade. In the USA, cases of visual impairment and blindness due to age-related macular degeneration (ARMD) are expected to increase from 620,000 cases in 2010 to 1.7 million in 2050 [1]. While therapeutic agents are currently available for treating only the wet form of ARMD, new treatments are anticipated in the future for treating the more prevalent dry form of ARMD [2]. The global ophthalmic pharmaceutical market with registered sales of US$14 billion in 2009, is forecasted to grow at a double digit rate [3].

Improving Melatonin Delivery Within the Eye

“…Melatonin and analogues can be soaked in contact lenses overnight and the lenses can be fitted to obtain a sustained release of these substances. In this way, when melatonin is topically instilled it lasted no more than 2 min on the ocular surface as happens with all compounds applied in this way [18]. When melatonin and analogues are released from contact lenses the maximal release occurs 2 hours after the lens fitting, their presence being measurable for more than 300 min, as it happens with other naturally occurring substances [27].…”

“…A possible alternative for a long-term drug delivery is the use of contact lenses, in such a way, ocular bioavailability will be improved considering reduced tear mixing between the lens and the cornea besides the extended drug release [26]. The traditional method is to soak the lens in drug solution in order for the drug to be absorbed into the polymeric lenses, this way permits limited and slow release of the drugs into the post-lens lacrimal fluid [18,27]. Melatonin and analogues can be soaked in contact lenses overnight and the lenses can be fitted to obtain a sustained release of these substances.…”

“…Treating ocular conditions have many challenges due to poor drug delivery because of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva [18]. While topical ocular bioavailability is extraordinary poor, in the order of 5% or less, sustained delivery systems for diseases of the posterior segment such as various vitreoretinal disorders through intraocular delivery systems are used via implantable devices or injections [19].…”

An approach to revolutionize cataract treatment by enhancing drug probing through intraocular cell line

“…The main way of administering a drug for any eye disorder is ophthalmic application but the conventional formulations ensure only a limited amount of drug penetrating these barriers. Although eye is generally protected, but still problems relating to age like cataract frequently surface and treatment of cataract generally leads to a single outcome – surgery [2] and intravitreal procedures associated with numerous side effects like detachment of retina [3]. Cataract may be the chief cause of blindness in 50% of cases worldwide.…”

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

“…Eye diseases are often treated by topically administered drugs. However, as commented in section 2.1.9, ocular drug delivery is strongly limited by the barriers of the eye resulting in poor drug bioavailability (Kompella et al, 2010). The cornea is a chemical and mechanical barrier that stops the entry of any foreign body, included drugs, to the anterior chamber (Leong and Tong, 2015).…”