Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

Abstract

The treatment of the posterior-segment ocular diseases, such as age-related eye diseases (AMD) or diabetic retinopathy (DR), present a challenge for ophthalmologists due to the complex anatomy and physiology of the eye. This specialized organ is composed of various static and dynamic barriers that restrict drug delivery into the target site of action. Despite numerous efforts, effective intraocular drug delivery remains unresolved and, therefore, it is highly desirable to improve the current treatments of diseases affecting the posterior cavity. This review article gives an overview of pharmacokinetic and biopharmaceutics aspects for the most commonly-used ocular administration routes (intravitreal, topical, systemic, and periocular), including information of the absorption, distribution, and elimination, as well as the benefits and limitations of each one. This article also encompasses different conventional and novel drug delivery systems designed and developed to improve drug pharmacokinetics intended for the posterior ocular segment treatment.

Keywords: intravitreal administration; ocular drug delivery systems; ocular pharmacokinetics; ocular routes of drug administration; topical administration.

Figure 1

Prevalence of the main ocular pathologies. Data from the world report on vision published by the World Health Organization (WHO), 2019 [1].

Figure 2

The first image represents a scheme of the different routes of drug administration to the posterior segment (dots symbolize the injection site of each route), while second image exemplifies the anatomy of the eye.

Figure 3

Schematic drawing of the sclera, choroid, and retina.

Figure 4

Schematic representation of the anterior and posterior clearance from the vitreous humor.

Figure 5

Schematic representation of the human corneal layers.

Figure 6

Blood–aqueous barrier (BAB) structure.

Figure 7

Different topical routes of drug absorption from the cornea/conjunctiva to the vitreous humor: Periocular route marked in green. Uvea-scleral route in blue. Transvitreal route marked in orange.