Permeation of Proteins, Oligonucleotide and Dextrans Across Ocular Tissues: Experimental Studies and a Literature Update

Corneal and scleral permeability of Desmoteplase in different species

“…The results of drug permeability studies can therefore not be extrapolated from one species to others. 24,25,28,44,45 Nevertheless, we expected lower drug permeation in species with thicker tissues and higher values in species with a thinner cornea and sclera. However, those expected trends were not confirmed in this study.…”

“…DSPA permeation experiments in Franz-type diffusion cells were performed as described previously (Figure 1; SES GmbH-Analysesysteme). 24,35 The donor compartment was filled with 300 µL of 1.4 mg/ mL DSPA (pH 7.5, 0.027 mmol/L) or HEPES buffer for negative controls only (n = 2, rabbit cornea and sclera). The receiving phase consisted of 5 mL 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES buffer, 10 mmol/L, pH 7.4, 140 mmol/L NaCl), 12 thermostated at 37°C, and stirred with a magnetic bar.…”

“…Precorneal factors (solution drainage, blinking, tear film composition, and turnover) and anatomical barriers including the various layers of the cornea, conjunctiva, and sclera as well as their thickness and surface area play an important role in drug permeation. [22][23][24][25][26] The cornea is considered to be the main route of permeation after topical application of drugs, but larger molecules permeate the eye mainly by diffusion through the sclera. 22,24,25,[27][28][29][30] The epithelium with its intercellular tight junctions represents the first barrier to pass; hydrophilic, small molecules have been shown to permeate between cells, whereas the transcellular route contributes to epithelial transfer of lipophilic drugs.…”

“…[22][23][24][25][26] The cornea is considered to be the main route of permeation after topical application of drugs, but larger molecules permeate the eye mainly by diffusion through the sclera. 22,24,25,[27][28][29][30] The epithelium with its intercellular tight junctions represents the first barrier to pass; hydrophilic, small molecules have been shown to permeate between cells, whereas the transcellular route contributes to epithelial transfer of lipophilic drugs. The epithelium is a rate-limiting barrier for highly polar, high-MW drugs and contributes 90% of the barrier for hydrophilic substances.…”

Preclinical Development of RNAi-Inducing Oligonucleotide Therapeutics for Eye Diseases

“…Drugs can take two paths to penetrate the corneal epithelium: the intracellular path crossing through the cells or the paracellular path bypassing between cells. The cells of the corneal epithelium are tightly attached to each other with gap and tight junctions that restrict the diffusion of large molecules between them [52][53][54]. The cross-cellular pathway requires molecules to be able to cross cell membranes; thus, lipophilic molecules have an easier access through this route.…”