The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye

Abstract

The prevalence of chronic fundus diseases is increasing with the aging of the general population. The treatment of these intraocular diseases relies on invasive drug delivery because of the globular structure and multiple barriers of the eye. Frequent intraocular injections bring heavy burdens to the medical care system and patients. The use of topical drugs to treat retinal diseases has always been an attractive solution. The fast development of new materials and technologies brings the possibility to develop innovative topical formulations. This article reviews anatomical and physiological barriers of the eye which affect the bioavailability of topical drugs. In addition, we summarize innovative topical formulations which enhance the permeability of drugs through the ocular surface and/or extend the drug retention time in the eye. This article also reviews the differences of eyes between different laboratory animals to address the translational challenges of preclinical models. The fast development of in vitro eye models may provide more tools to increase the clinical translationality of topical formulations for intraocular diseases. Clinical successes of topical formulations rely on continuous and collaborative efforts between different disciplines.

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

“…Due to certain beneficial properties, such as avoidance of systemic absorption, as well as hepatic metabolism and ease of drug administration, the topical route is preferred to treat superficial infections and inflammation, besides conditions such as glaucoma or uveitis that affect the anterior segment of the eye [ 9 , 10 ]. It has been stated that the ocular bioavailability from topical solution is only 5–10% due to reduced entry of drugs to inner ocular tissues; it is difficult to attain targeted drug concentration, particularly into the posterior segment [ 11 ].…”

Topical Drug Delivery to the Posterior Segment of the Eye

“…Besides the transcorneal diffusion through the anterior chamber to the vitreous and retina, topically applied drugs can also enter the systemic circulation and reach the retina via retinal vasculatures [45]. This periocular drug absorption includes diffusion of the drug through the conjunctiva to the Tenon's capsule and, further, through the sclera and choroid to the retina.…”

“…Choosing the suitable preclinical model is of utmost importance, as shown by repeated failures of topically applied drugs in clinical investigations, in spite of promising preclinical data in rodents [52]. Animal models used in ocular drug delivery studies include mice, rats, rabbits, monkeys, and sometimes dogs and pigs [45]. There are various characteristics that can be taken into account.…”

“…The bioavailability of topically applied drugs at the back of the eye can be influenced, among other factors, by differences in the thickness of cornea and sclera, axial length, and vitreous volume. The human vitreous volume as an example is one thousand times larger than in rodents, which may have a strong influence on the intraocular concentration of small molecule drugs applied via eye drops [45].…”

“…Ocular characteristics of commonly used preclinical models vs. the human eye (modified and supplemented according to Wang et al[45]). …”