Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide.
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.
Ouchi
Tatsuro
T
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita Osaka 564-8680, Japan. touchi@ipcku.kansai-u.ac.jp
Yamabe
Etsuro
E
Hara
Kei
K
Hirai
Mikiko
M
Ohya
Yuichi
Y
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
C114557:5-carboxytetramethylrhodamine succinimidyl ester; D012235:Rhodamines; D001360:Avidin; D005690:Galactose