Permeation of proteins, oligonucleotide and dextrans across ocular tissues: experimental studies and a literature update.

Proteins and oligonucleotides represent powerful tools for the treatment of several ocular diseases, affecting both anterior and posterior eye segments. Despite the potential of these compounds, their administration remains a challenge. The last years have seen a growing interest for the noninvasive administration of macromolecular drugs, but still there is only little information of their permeability across the different ocular barriers. The aim of this work was to evaluate the permeation of macromolecules of different size, shape and charge across porcine ocular tissues such as the isolated sclera, the choroid Bruch's membrane and the cornea, both intact and de-epitelialized. Permeants used were two proteins (albumin and cytochrome C), an oligonucleotide, two dextrans (4 and 40 kDa) and a monoclonal antibody (bevacizumab). Obtained data and its comparison with the literature highlight the difficulties in predicting the behavior of macromolecules based on their physicochemical properties, because the interplay between the charge, molecular radius and conformation prevent their analysis separately. However, the data can be of great help for a rough evaluation of the feasibility of a noninvasive administration and for building computational models to improve understanding of the interplay among static, dynamic and metabolic barriers in the delivery of macromolecules to the eye.