title: Improved corneal toxicity and permeability of tranilast by the preparation of ophthalmic formulations containing its nanoparticles.
abstract: We prepared ophthalmic formulations containing 0.5% tranilast (TL) nanoparticles using 0.005% benzalkonium chloride (BAC), 0.5% D-mannitol, and 2-hydroxypropyl-β-cyclodextrin (HPβCD), and investigated their usefulness in the ophthalmologic field by evaluating corneal toxicity and permeability. TL nanoparticles were prepared using zirconia beads and Bead Smash 12, which allowed the preparation of high quality dispersions containing 0.5% TL nanoparticles (particle size, 34 ± 20 nm, means ± S.D.). Dispersions containing TL nanoparticles are tolerated better by human corneal epithelium cells than a commercially available 0.5% TL preparation (RIZABEN(®) eye drops). In addition, the addition of TL nanoparticles to the dispersions does not affect the antimicrobial activity of BAC against Escherichia coli (ATCC 8739), and the corneal penetration of TL from dispersions containing TL nanoparticles was significantly higher than in the case of the commercially available 0.5% TL eye drops. It is possible that dispersions containing TL nanoparticles will show increased effectiveness against ocular inflammation, and that ocular drug delivery systems using drug nanoparticles may lead to an expansion of their usefulness for therapy in the ophthalmologic field.
authors.affiliation: Faculty of Pharmacy, Kinki University.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nagai
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ono
authors.forename: Miho
authors.initials: M
authors.lastname: Hashino
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
authors.forename: Norio
authors.initials: N
authors.lastname: Okamoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems; D024881:Drug Resistance, Bacterial; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008297:Male; D053758:Nanoparticles; D009883:Ophthalmic Solutions; D011817:Rabbits; D015040:Zirconium; D062367:ortho-Aminobenzoates / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D009883:Ophthalmic Solutions; D062367:ortho-Aminobenzoates; D015040:Zirconium; C012293:tranilast; C028541:zirconium oxide