| Abstract (english) | Ocular barriers effectively protect the eye from pharmaceuticals. The development
of strategies to overcome these barriers in order to improve ocular drug delivery
remains a major challenge for pharmaceutical sciences. The aim of the present work
is to describe the current models of the ocular barriers (cornea, conjunctiva, sclera,
blood-aqueous barrier, blood-retinal barrier).
In vitro cell culture models have been used to study passive drug permeation and
active drug transport across different ocular barriers as well as for toxicological screening
of compounds as alternative to in vivo toxicity tests. Primary cell cultures and
immortalized cell lines as in vitro models of ocular barriers are reviewed herein.
Primary cell cultures (e.g. cornea, conjunctiva, retina) of different origin (e.g.
human, rabbit, rat, bovine, porcine) are described. lmmortalized cell lines derived
from corneal epithelial, conjunctival epithelial and retinal pigment epithelial cells
have some advantages (the tissue isolation and cell purification is not required,
growing after a large number of passages, revive after storage in liquid nitrogen) as
well as disadvantages (potential abnormal characteristics, different gene expression
profile) over primary cells. However, much work still needs to be done in order to
develop cell-based permeability models of the ocular barriers for large scale screening
of pharmaceutical compounds and formulations.
Ex vivo tissue models have been used to study drug permeation across freshly
excised biological ocular barriers such as cornea, conjunctiva, sclera, retinal pigment epithelium, neural retina. The results of drug permeability experiments with excised
animal tissue are often less reproducible (species related applicability problems) in
comparison to cell-based permeability experiments. Although the tissue based models
represent low-throughput assay, this model provides a better prediction of in vivo
ocular drug bioavailability in comparison to cell-based models.
ln vivo animal experiments have been used for pharmacokinetic studies and
ocular tolerance evaluations. The experiments are usually conducted on rabbits as
commonly used animal model. In most cases rabbits have to be sacrificed at each
time-point to collect samples in ocular pharmacokinetic studies. Therefore, animal
experiments are often criticized for ethical and economical reasons. In this paper the
different modifications of the classical pharmacokinetic scudies are presented. The
ocular pharmacokinetics can be studied by analyzing the drug concentrations into
tear fluid, aqueous humor and different ocular tissues. Furthermore, the pharmacological
or side effect can be determined as indirect measure of the ocular drug
bioavailability. The commonly used Draize test for the ocular tolerance evaluation is
briefly described. |
