title: Permeation of proteins, oligonucleotide and dextrans across ocular tissues: experimental studies and a literature update.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of Parma, Parma, 43124, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pescina
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, 43126, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Govoni
authors.affiliation: Centre for Drug Research, University of Helsinki, Helsinki, FI-00014, Finland.
authors.forename: Maxim
authors.initials: M
authors.lastname: Antopolsky
authors.affiliation: Department of Chemistry, Aalto University, Aalto, FI-00076, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Murtomäki
authors.affiliation: Department of Pharmacy, University of Parma, Parma, 43124, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Padula
authors.affiliation: Department of Pharmacy, University of Parma, Parma, 43124, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Santi
authors.affiliation: Department of Pharmacy, University of Parma, Parma, 43124, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
mesh_terms: D000818:Animals; D000068258:Bevacizumab / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002829:Choroid / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D004058:Diffusion; D005260:Female; D008297:Male; D009841:Oligonucleotides / Q000378:metabolism*; D010539:Permeability; D011506:Proteins / Q000378:metabolism*; D012590:Sclera / Q000378:metabolism*; D013552:Swine
chemical_list: D003911:Dextrans; D009841:Oligonucleotides; D011506:Proteins; D000068258:Bevacizumab
keywords: diffusion; in vitro models; macromolecular drug delivery; monoclonal antibody; oligonucleotides; passive diffusion/transport; permeability; proteins