title: Folate-appended β-cyclodextrin as a promising tumor targeting carrier for antitumor drugs in vitro and in vivo.
abstract: A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c(2)-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c(2)-β-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (>10(6) M(-1)). Cellular uptake of DOX was increased by the addition of Fol-c(2)-β-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c(2)-β-CyD increased in vitro antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c(2)-β-CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c(2)-β-CyD could be useful as a promising antitumor drug carrier.
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors: Ayaka
authors: A
authors: Okamatsu
authors: Keiichi
authors: K
authors: Motoyama
authors: Risako
authors: R
authors: Onodera
authors: Taishi
authors: T
authors: Higashi
authors: Takahiro
authors: T
authors: Koshigoe
authors: Yasutaka
authors: Y
authors: Shimada
authors: Kenjiro
authors: K
authors: Hattori
authors: Tomoko
authors: T
authors: Takeuchi
authors: Hidetoshi
authors: H
authors: Arima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002208:Caproates / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002208:Caproates; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D005492:Folic Acid; C031215:betadex