(Circulation. 1996;94:1441-1448.)
© 1996 American Heart Association, Inc.
Articles |
Local Intraluminal Infusion of Biodegradable Polymeric Nanoparticles
A Novel Approach for Prolonged Drug Delivery After Balloon Angioplasty
the Department of Cardiology, Center for Thrombosis and Vascular Biology, the Cleveland Clinic Foundation, Cleveland, Ohio (L.A.G., Y.J., A.M.L., E.J.T.), and the Division of Pediatric Cardiology, the University of Michigan Medical School, Ann Arbor (V.L., C.S., R.L.).
Correspondence to Eric J. Topol, MD, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195-5066.
Background Several perfusion balloon catheters are under investigation for local drug delivery; however, sustained tissue drug levels are difficult to achieve with these techniques. To overcome this problem, sustained-release, biodegradable nanoparticles represent a potential alternative for prolonged local delivery.
Methods and Results A biodegradable polylactic-polyglycolic acid (PLGA) copolymer was used to formulate nanoparticles. Fluorescent-labeled nanoparticles were intraluminally administered in a single, 180-second infusion after balloon injury in the rat carotid model. Localization and retention at different time points and biocompatibility of nanoparticles were evaluated. To evaluate the potential of the system in the prevention of neointimal formation, dexamethasone was incorporated into the particles and delivered locally as above. Nanoparticles were seen in the three layers of the artery at 3 hours and 24 hours. At 3 days, they were mainly present in the adventitial layer, decreasing at 7 days, with no fluorescent activity at 14 days. The PLGA nanoparticles appeared to be fully biocompatible. In the dexamethasone nanoparticle study, a significant amount of dexamethasone was present in the treated segment for up to 14 days after a single infusion, with no plasma levels detected after the first 3 hours. There was a 31% reduction in intima-media ratio in animals treated with local dexamethasone nanoparticles compared with control.
Conclusions Nanoparticles successfully penetrated into the vessel wall and persisted for up to 14 days after a short, single intraluminal infusion. Local administration of nanoparticles with incorporated dexamethasone significantly decreased neointimal formation. This methodology appears to have important potential for clinical applications in local drug delivery.
Key Words: nanoparticles • arteries • balloons • angioplasty • drugs
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