Intraarterial protein delivery via intimally-adherent bilayer hydrogels

Arterial structure plays an important role in drug delivery from intraarter ial depots. The internal elastic lamina forms a major diffusive resistance to the transport of macromolecular drugs from intimally-adherent hydrogel d epots to the arterial media. The objectives of this study were to develop a n approach by which to form a bilayer hydrogel depot with a higher permeabi lity intimally-adherent layer, containing the drug, and a lower permeabilit y luminal layer, and to evaluate ex vivo whether this luminal layer could e nhance the delivery of a protein to the arterial media. Sequential interfac ial photopolymerization of polyethyleneglycol diacrylate precursors (molecu lar weight 4000 for the luminal layer, 10,000 for the intimal layer) with e osin Y and triethanolamine as an initiation system was employed to form the se bilayer hydrogels. Horseradish peroxidase was used as a model protein, a nd delivery to the arterial media was measured in rat carotid arteries ex v ivo. The lower permeability luminal layer served to enhance delivery of the model protein into the arterial media for delivery periods at least up to 72 h. Thus, it was possible to compensate for the diffusional resistance of the internal elastic lamina on the one side of the hydrogel depot with a s econd diffusional resistance on the other side of the hydrogel. (C) 2000 El sevier Science B.V. All rights reserved.