Direct intraarterial wall injection of microparticles via a catheter: a potential drug delivery strategy following angioplasty.
Local delivery into the arterial wall of medications at high concentrations may evolve as a method to reduce postangioplasty restenosis. However, since the atherosclerotic artery has increased vasa vasorum, medications injected in a fluid state may diffuse out of the arterial wall too quickly to have a therapeutic effect. Thus we evaluated whether microparticles as a model for a particulate microcarrier drug delivery system, injected via a porous balloon catheter, could be retained within the atherosclerotic rabbit femoral arterial wall. Arteries were injected with a 5 microns microparticle suspension for 45 seconds at either 3 or 5 atm of infusion pressure immediately following balloon angioplasty. Arteries were obtained immediately following the procedure or at 1, 3, 7, or 14 days after infusion to evaluate for the presence of retained microparticles. Of 34 arteries, 30 contained retained microparticles, with 21 exhibiting microparticles in the neointimia, 12 in the media, and 25 in the adventitia. Microparticles were retained for as long as 14 days, and there was no difference between the distribution or quantity of microparticles at 3 or 5 atm of infusion pressure. The mode of microparticle distribution probably involved deposition within dissection planes, although evidence for vasa vasorum transport was observed. We hypothesize that biodegradable microparticles could serve as a vehicle for intramural drug delivery in the treatment of restenosis.
Wilensky
R L
RL
Krannert Institute of Cardiology, Indianapolis, IN 46202.
March
K L
KL
Hathaway
D R
DR
D000800:Angioplasty, Balloon; D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000628:therapy; D016503:Drug Delivery Systems / Q000379:methods; D005240:Feasibility Studies; D007269:Injections, Intra-Arterial; D015552:Injections, Intralesional; D008863:Microspheres; D011817:Rabbits; D012008:Recurrence; D013997:Time Factors