Effects of poly-L-arginine on the permeation of hydrophilic compounds through surface ocular tissues.
We investigated whether poly-L-arginine (PLA) could improve permeation of the hydrophilic compounds, FITC-labeled dextran (MW 3800, FD-4) and pyridoxamine, through ocular surface tissues. Samples of cornea, conjunctiva, or conjunctiva/sclera composite from Japanese white rabbits were mounted in Ussing chambers to measure FD-4 and pyridoxamine permeation and transepithelial electric resistance (TEER). The integrity and viability of the conjunctiva were assessed by chronological TEER monitoring and MTT assay, respectively. The permeability coefficient (Papp) of FD-4 in the cornea, conjunctiva, and conjunctiva/sclera composite was increased by the addition of PLA (MW 38 kDa, PLA (50) at 0.1 mg/ml by 6.81-, 9.78-, and 7.91-fold, respectively. The Papp of pyridoxamine was also increased in the presence of PLA (50) by 7.98-, 4.67-, 8.31-fold, respectively. A corresponding reduction in TEER was observed in all tissues. However, the reduced TEER in the case of the conjunctiva had recovered to ca. 70% 120 min after replacing the mucosal fluid with fresh bicarbonated Ringer's solution. MTT assay results indicated that treatment of the conjunctiva with 0.1 mg/ml PLA (50) did not change the production of formazan compared to that without PLA (50), indicating that the conjunctival viability is not significantly affected by PLA (50). Our findings suggest that PLA may be useful in promoting the ocular delivery of hydrophilic drugs without producing significant epithelial damage.
Nemoto
Eiichi
E
Takahashi
Hirokazu
H
Kobayashi
Daisuke
D
Ueda
Hideo
H
Morimoto
Yasunori
Y
D000818:Animals; D002021:Buffers; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics; D004553:Electric Conductivity; D004594:Electrophysiology; D005123:Eye / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D010455:Peptides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011107:Polylysine / Q000494:pharmacology; D011733:Pyridoxamine / Q000493:pharmacokinetics; D011817:Rabbits; D012590:Sclera / Q000187:drug effects / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D002021:Buffers; D003911:Dextrans; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; C015219:fluorescein isothiocyanate dextran; D011107:Polylysine; C015462:polyarginine; D011733:Pyridoxamine; C022616:thiazolyl blue; D016650:Fluorescein-5-isothiocyanate