Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?

Abstract

Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.

Angiostatins modulate ACE2 and GFAP levels in injured rat cornea and do not affect viability of retinal pigment epithelial cells

“…Considering the surface location of the satellite glial cells in the eye, K5 is able to target these cells more readily in comparison with K1-3 because of a relatively small size of the molecule. It is known that the drugs instilled onto the ocular surface during topical ophthalmic administration can reach the posterior segment of the eye and affect the retinal cells even in small concentrations [39]. The results of MTT assay with the use of RPE cells confirm non-toxici-ty of both tested AS types for the retinal epithelium.…”

Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds

“…This mode of transport has been demonstrated with insulin administration in rabbits [ 33 , 34 ]. This phenomenon has invigorated the discussion around the topical administration of medicines to treat diseases affecting the posterior of the eye, such as AMD and DR [ 35 , 36 ], although whether such an approach will prove clinically efficacious remains to be determined.…”

Scalability of Pharmaceutical Co‐Crystal Formation by Mechanochemistry in Batch

“…[22] However, around 90 % of preclinical compounds APIs in the development pipeline are poorly soluble and present bioavailability challenges. [23][24] Therefore, the industrial interest in the preparation of pharmaceutical co-crystals as marketable drugs is growing, together with the need of sustainable methods for their clean manufacturing, to fulfill the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal objectives. For these reasons, the preparation of pharmaceutical materials, including co-crystals, by mechanochemical methods is a valuable and sustainable approach, [4,8] also considering some of the peculiarities of this powder-based technology, allowing: i) scalability, [8,10,11,[25][26] ii) generally higher productivity compared to solution based procedures, and iii) to circumvent issues related to solubility, sometimes encountered in solution synthesis and crystallisation, allowing to access compounds otherwise impossible to be obtained, [2][3][4][5][6][7]27] or not displaying the suitable (e. g. tabletability) and biopharmaceutical (e. g. dissolution rate) properties.…”

“…However, around 90 % of preclinical compounds APIs in the development pipeline are poorly soluble and present bioavailability challenges [23–24] . Therefore, the industrial interest in the preparation of pharmaceutical co‐crystals as marketable drugs is growing, together with the need of sustainable methods for their clean manufacturing, to fulfill the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal objectives.…”