Pharmacokinetic aspects of retinal drug delivery

Abstract

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.

Spectral‐domain optical coherence tomography imaging of normal foveae: A pilot study in 17 diurnal birds of prey

“…Cone photoreceptors require more energy than rods . As the pecten appears to be associated with providing nourishment and oxygen supply to the retina and as the vitreous allows relatively molecular mobility, it is possible that the closer proximity of the central fovea to the pecten is beneficial due to the higher energy needs of the central fovea . Photoreceptors and retinal pigment epithelium (RPE) are responsible for phototransduction, which require a large amount of energy; therefore, it would not be surprising if the central fovea had higher energetic requirements given its functionality and metabolic requirements .…”

Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles

“…We believe that the results are promising, considering that the concentration of HA‐PGG graft copolymer in the vitreous could be around 0.125 mg mL −1 after intravitreal injection. The volume of the human vitreous is ≈4 mL and the maximum volume for intravitreal injection is 50 µL . Assuming a concentration of 10 mg mL −1 for HA‐PGG graft copolymer, which is not very viscous yet, one injection could yield 500 µg of administered graft copolymer.…”

“…A water soluble delivery vehicle could overcome certain limitations associated with particles or implants, such as visual disturbances, aggregation, increased ocular pressure and other adverse ocular effects . Furthermore, drug release and degradation rate of implants or polymer particles need to be carefully synchronized to avoid the accumulation of “ghost” devices inside the eye …”

“…Second, with the use of special linkages the potential drugs could be released from grafts after cell uptake . The release of drug‐carrying grafts prior to the release of drugs would reduce their cytotoxic effects in the eye and minimize drug clearance through the blood‐ocular barriers . Compared with nanoparticles, short polymer chains have higher diffusivity and higher permeation into the retinal layers …”

Intracellular enzymes of the retinal pigment epithelial cells for controlled drug delivery

“…Chronic intraocular injections, however, are invasive causing a burden to the healthcare providers and patients. Furthermore, the vitreal half-lives of most drugs are in the hours necessitating intravitreal injections at short dosing intervals (a few days) [2]. This is a difficult proposition in the clinical setting.…”