In vivo PEG modification of vascular surfaces for targeted delivery

• Published in: Journal of vascular surgery Vol. 55; no. 4; pp. 1087 - 1095
• Main Authors: Deglau, Timothy E., PhD, Maul, Timothy M., PhD, Villanueva, Flordeliza S., MD, Wagner, William R., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-04-2012; Elsevier
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Catheterization - methods; Disease Models, Animal; Drug Delivery Systems - methods; Emergency and intensive care: renal failure. Dialysis management; Female; Femoral Artery - drug effects; Femoral Artery - injuries; Graft Occlusion, Vascular - prevention & control; Intensive care medicine; Medical sciences; Microscopy, Fluorescence; Microspheres; Polyethylene Glycols - pharmacology; Postoperative Complications - prevention & control; Rabbits; Random Allocation; Reference Values; Sensitivity and Specificity; Surface Properties; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Thrombosis - prevention & control; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Vascular Surgical Procedures - adverse effects; Vascular Surgical Procedures - methods; Wound Healing - physiology; Vascular disease; Ethylene oxide polymer; Cardiovascular disease; Thrombosis; Surgery
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2011.09.081

Objective Thrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin. Methods Rabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small-diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epifluorescence microscopy at 0, 24, 48, and 72 hours. Results Polymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small-diameter tube with similar results. Maximum polymer coverage occurred at 0 hours and decreased to 85% maximal at 24 hours, 72% at 48 hours, and 67% at 72 hours. The initial number of microspheres per mm2 binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control ( P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 hours, respectively; while nonspecific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm2 as opposed to 26 microspheres/mm2 for the unmodified, healthy controls ( P < .01). Conclusions Chemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified, or healthy vascular surfaces.