Print Email Facebook Twitter Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall Title Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall Author Sakharov, D.V. Jie, A.F.H. Bekkers, M.E.A. Emeis, J.J. Rijken, D.C. Gaubius Instituut TNO Publication year 2001 Abstract We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is based on the concept of a bifunctional drug comprising a "therapeutic effector" and an "affinity vehicle," which should bind to an abundant component of the vessel wall. The aim of the present study was to select molecules suitable for the role of affinity vehicles for ECM-LDD and to study their intravascular delivery and retention ex vivo and in an animal model. By use of fluorescence microscopy, the following molecules were selected on the basis of strong binding to cross sections of human vessels: protamine, polylysine, polyarginine, a glycosaminoglycan-binding peptide from vitronectin, and a synthetic dendrimer. With polylysine as a prototypic affinity vehicle, we showed that after intravascular delivery, polylysine was concentrated throughout a luminal layer of the vascular wall to an extremely high concentration of 20 g/L and was retained therein for at least 72 hours of perfusion without noticeable losses. Low molecular weight (fluorescein) and high molecular weight (hirudin) compounds could be chemically conjugated to polylysine and were retained in the vessel wall after intravascular delivery of the conjugates. In conclusion, by use of the ECM-LDD method, an extremely high concentration and long-term retention of locally delivered drug can be reached. Polycationic molecules can be considered as potential affinity vehicles for ECM-LDD. Chemicals/CAS: Glycosaminoglycans; Hirudins; Peptides; polyarginine, 25212-18-4; Polylysine, 25104-18-1; Protamines; Vehicles Subject BiologyAnimalsAortaArterial Occlusive DiseasesArteriesCarotid ArteriesCulture TechniquesDrug Delivery SystemsExtracellular MatrixGlycosaminoglycansHirudinsHumansMaleMicroscopy, FluorescencePeptidesPolylysineProtaminesRatsRats, WistarUmbilical ArteriesVehicles To reference this document use: http://resolver.tudelft.nl/uuid:b896986b-113c-4fae-8472-80cb511859d4 TNO identifier 236345 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 21 (6), 943-948 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.