In vitro and ex vivo models to study drug delivery barriers in the posterior segment of the eye.

Many ocular disorders leading to blindness could benefit from efficient delivery of therapeutics to the retina. However, despite extensive research into drug delivery vehicles and administration techniques, efficacy remains limited because of the many static and dynamic barriers present in the eye. Comprehension of the various barriers and especially how to overcome them can improve our ability to estimate the potential of existent drug delivery vectors and support the design of new ones. To this end, this review gives an overview of the most important ocular barriers for each administration route to the back of the eye. For each barrier, its biological composition and its role as an obstacle towards macromolecules, nanoparticles and viral vectors will be discussed; special attention will be paid to the influence of size, charge and lipophilicity of drug(s) (carrier) on their ability to overcome each barrier. Finally, the most significant available in vitro and ex vivo methods and models to test the potential of a therapeutic to cross each barrier are listed.