title: Importance of the Direct Contact of Amorphous Solid Particles with the Surface of Monolayers for the Transepithelial Permeation of Curcumin.
abstract: The amorphization has been generally known to improve the absorption and permeation of poorly water-soluble drugs through the enhancement of the solubility. The present study focused on the direct contact of amorphous solid particles with the surface of the membrane using curcumin as a model for water-insoluble drugs. Amorphous nanoparticles of curcumin (ANC) were prepared with antisolvent crystallization method using a microreactor. The solubility of curcumin from ANC was two orders of magnitude higher than that of crystalline curcumin (CC). However, the permeation of curcumin from the saturated solution of ANC was negligible. The transepithelial permeation of curcumin from ANC suspension was significantly increased as compared to CC suspension, while the permeation was unlikely correlated with the solubility, and the increase in the permeation was dependent on the total concentration of curcumin in ANC suspension. The absorptive transport of curcumin (from apical to basal, A to B) from ANC suspension was much higher than the secretory transport (from basal to apical, B to A). In vitro transport of curcumin through air-interface monolayers is large from ANC but negligible from CC particles. These findings suggest that the direct contact of ANC with the absorptive membrane can play an important role in the transport of curcumin from ANC suspension. The results of the study suggest that amorphous particles may be directly involved in the transepithlial permeation of curcumin.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Sachiha
authors.initials: S
authors.lastname: Kasatani
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: M Technique Co., Ltd., 2-2-16 Technostage, Izumi, Osaka 594-1144, Japan.
authors.forename: Kaeko
authors.initials: K
authors.lastname: Araki
authors.affiliation: M Technique Co., Ltd., 2-2-16 Technostage, Izumi, Osaka 594-1144, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Enomura
authors.affiliation: School of Pharmacy, Shujitsu University , 1-6-1 Nishigawara, Naka, Okayama 703-8111, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: School of Pharmacy, Shujitsu University , 1-6-1 Nishigawara, Naka, Okayama 703-8111, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inoue
authors.affiliation: School of Pharmacy, Shujitsu University , 1-6-1 Nishigawara, Naka, Okayama 703-8111, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furubayashi
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasagi Nakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D053758:Nanoparticles / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D013535:Suspensions; D014867:Water; D003474:Curcumin
keywords: amorphous; curcumin; dispersion; nanoparticles; transepithelial permeation