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.

Cell attachment and growth on films prepared from poly(depsipeptide-co-lactide) having various functional groups.

In tissue engineering related to the regeneration of damaged or lost tissue, excellent biodegradable materials are desired as temporary scaffolds to support cell growth and then disappear with the progress of tissue regeneration. We previously synthesized biodegradable poly(depsipeptide-co-lactide), poly[(Glc-Asp)-co-LA], and poly[(Glc-Lys)-co-LA] with reactive side-chain groups. In this study, to evaluate the utility of these copolymers as functional scaffolds for tissue regeneration, the effects of reactive and ionic side-chain groups on cell attachment and growth were investigated using copolymer films with various numbers of carboxyl or amino groups. Poly[(Glc-Lys)-co-LA] and poly[(Glc-Asp)-co-LA] films having appropriate positive or negative charges exhibited higher cell attachment ability than did poly-L-lactide. Good cell growth was observed on the copolymer films. During cell culture, the copolymer films exhibited higher degradation rates related to the depsipeptide content. Biodegradable polymer matrices with reactive surfaces for cell growth successfully were prepared using copolymers with various numbers of depsipeptide units. Varying the depsipeptide unit numbers in the copolymer could change the degradation rate of these matrices.