title: In vivo PEG modification of vascular surfaces for targeted delivery.
abstract: 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 mm(2) 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/mm(2) as opposed to 26 microspheres/mm(2) 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.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Deglau
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Maul
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002404:Catheterization / Q000379:methods; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000293:injuries; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D008856:Microscopy, Fluorescence; D008863:Microspheres; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control; D014656:Vascular Surgical Procedures / Q000009:adverse effects / Q000379:methods; D014945:Wound Healing / Q000502:physiology
chemical_list: D011092:Polyethylene Glycols