Diffusion and clearance of drugs from the back of the eye
Mass transport within the eye is dominated by aqueous outflow through the front of the eye. Aqueous is constantly provided to nourish the cornea and lens so we can see.
Drugs injected into the back or posterior segment of the eye by intravitreal injection clear by diffusion from the vitreous.
Large, highly charged biological molecules such as therapeutic antibodies diffuse slowly through the vitreous. Biological based medicines are not membrane permeable, so they do not clear through the retina. They clear by the anterior pathway, which occurs by the drug diffusing from the vitreous into the front or anterior segment of the eye driven by the aqueous outflow.
Low molecular weight drugs diffuse more rapidly than large molecules through the vitreous. If a drug is permeable through membranes, it will clear through both the back of the eye via the retina (known as the retinal-choroid-sclera, RCS, pathway) and the front of the eye (known as the anterior hyaloid pathway) driven by aqueous outflow via the anterior pathway.
The PK-Eye™ accurately estimates the human intravitreal clearance time of drugs from the eye. The PK-Eye™ is being used to accelerate the development of intraocular drugs.
There is no approved model reported in the pharmacopeia specifically designed to determine intraocular pharmacokinetic of therapeutic proteins.
In research, little has been reported to develop an in vitro model that accounts for the aqueous flow to estimate clearance times for molecules that exit the eye predominantly via the anterior route.
A robust and simple-to-use in vitro model must address the inherent limitations of in vivo models and is required to develop long acting protein formulations for intraocular use.