title: Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide.
abstract: Recent studies have focused on the active targeting of drug delivery by combining a homing device and antitumor drug. For this purpose, synthesis of a well-designed vehicle (such as polymer/drug conjugates or nanoparticles) carrying a drug and a homing device requires many steps. We propose a new type of drug delivery system (DDS) by formation of a complex containing avidin (Av) plus biotinyl drug with a biotinyl homing device, which easily accommodates the combination of various drugs and homing devices. The targetable drug complex can be prepared by selecting an appropriate biotinyl drug derivative and a biotinyl homing device and mixing them with avidin. Fluorescent dye with 5-(and-6)-carboxytetramethylrhodamine (TAMRA) was used as a drug model, and galactose (Gal) recognized by liver parenchymal cells was used as a homing device. TAMRA and galactose were attached to biotin (Bio) through a triethyleneglycol (TEG) spacer group to give Bio-TEG-TAMRA conjugate and Bio-TEG-Gal conjugate, respectively. Confocal laser scanning microscopic studies suggest that the complexes prepared by mixing Bio-TEG-Gal conjugate and fluorescein isothiocyanate (FITC)-labeled Av (feed molar ratio 4:1), and mixing Bio-TEG-Gal conjugate, Bio-TEG-TAMRA conjugate and FITC-labeled Av are internalized into the hepatoma cells through a receptor-mediated endocytosis mechanism.
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita Osaka 564-8680, Japan. touchi@ipcku.kansai-u.ac.jp
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ouchi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yamabe
authors.forename: Kei
authors.initials: K
authors.lastname: Hara
authors.forename: Mikiko
authors.initials: M
authors.lastname: Hirai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohya
mesh_terms: D001360:Avidin / Q000138:chemical synthesis* / Q000378:metabolism; D019921:Biotinylation / Q000379:methods*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005690:Galactose / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D012235:Rhodamines / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: C114557:5-carboxytetramethylrhodamine succinimidyl ester; D012235:Rhodamines; D001360:Avidin; D005690:Galactose