Electro-encapsulating drugs within blood platelets: local delivery to injured arteries during angioplasty.
Prostacyclins (PGl2) inhibit platelet-platelet interactions at concentrations that do not affect platelet adhesion to collagen and other arterial subendothelial structures exposed during injury. Such compounds can be encapsulated within platelets by reversible electroporation and, using the platelet's natural haemostatic propensity, they can be targeted to injured vessels in vivo. In rat (aorta), rabbit (ileofemoral) and pig (carotid) angioplasty models, autologous platelets, electro-loaded with the stable prostacyclin iloprost and given intravenously after balloon overstretch injury, substantially reduced platelet deposition at the lesion site as compared with control platelets. In the pig model, when the drug-loaded platelets were delivered directly to the injury site during angioplasty via a double balloon delivery catheter, platelet deposition was restricted to monolayer coverage (> 80% reduction compared with controls). Candidate antiproliferative drugs (for co-encapsulating with iloprost) are being investigated in order to develop a combined antithrombotic/antirestenosis strategy for use during angioplasty and thrombolysis procedures. Autologous platelets as drug-targeting vehicles should obviate many of the immunological, toxicological and biodegradability concerns inherent in the use of other drug transport vectors such as antibodies, viruses, liposomes and synthetic polymer microcapsules.
Crawford
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Department of Rheumatology, Royal Free Hospital and School of Medicine, Hampstead, London, UK.
Chronos
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N
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000517:prevention & control; D001158:Arteries / Q000187:drug effects / Q000293:injuries*; D001792:Blood Platelets; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D013552:Swine; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control
D004337:Drug Carriers; D010975:Platelet Aggregation Inhibitors; D016285:Iloprost