Ocular membrane permeability of hydrophilic drugs for ocular peptide delivery.
The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl beta-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.
Sasaki
H
H
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Ichikawa
M
M
Yamamura
K
K
Nishida
K
K
Nakamura
J
J
D000818:Animals; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D004058:Diffusion; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009578:Nitrobenzenes / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D010539:Permeability; D011817:Rabbits; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
C105659:4-nitrophenyl cellopentaoside; D009578:Nitrobenzenes; D009844:Oligosaccharides; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone