Intraarterial protein delivery via intimally-adherent bilayer hydrogels

Abstract

Arterial structure plays an important role in drug delivery from intraarterial depots. The internal elastic lamina forms a major diffusive resistance to the transport of macromolecular drugs from intimally-adherent hydrogel depots to the arterial media. The objectives of this study were to develop an approach by which to form a bilayer hydrogel depot with a higher permeability intimally-adherent layer, containing the drug, and a lower permeability luminal layer, and to evaluate ex vivo whether this luminal layer could enhance the delivery of a protein to the arterial media. Sequential interfacial photopolymerization of polyethyleneglycol diacrylate precursors (molecular weight 4000 for the luminal layer, 10,000 for the intimal layer) with eosin Y and triethanolamine as an initiation system was employed to form these bilayer hydrogels. Horseradish peroxidase was used as a model protein, and delivery to the arterial media was measured in rat carotid arteries ex vivo. 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 second diffusional resistance on the other side of the hydrogel.