Inhibition of platelet recruitment to arterial lesions by predeposition of platelets containing encapsulated iloprost.
Drugs can be encapsulated within blood platelets by reversible electroporation and can be haemostatically targeted to vessel wall injury sites. Initial studies with iloprost-loaded pig platelets and pig aorta tunica media in perfusion circuits are presented. After autologous reconstitution into blood, no significant difference was observed in the deposition of 111Indium labelled sham-loaded and untreated platelets onto the tunica media during perfusion under low and high shear conditions. In paired experiments (n = 10 pairs), the deposition of iloprost-loaded platelets was significantly lower (mean 61%) after 5 min perfusion than the deposition from blood containing sham-loaded (control) platelets. A similar significant reduction (mean 54%) was seen after 10 min perfusion. Pre-perfusion of iloprost-loaded platelets for 10 min under low shear conditions (212/s), followed by 5 min perfusion of 111Indium labelled normal platelets, significantly reduced the secondary platelet deposition (p < 0.01) when compared with the deposition seen when control untreated platelets were preperfused. Significant differences (p < 0.001) in secondary deposition were also observed when primary and secondary platelet perfusions were made under high shear (1690/s). Histology of the tunica media segments post perfusion, supported the inhibitory effect of predeposited iloprost-loaded platelets on secondary platelet recruitment. By exploiting their natural haemostatic propensity, drug-loaded platelets can be targeted to vessel wall injury sites. Appropriate drugs could be packaged that may passivate the carrier platelets at the lesion inhibiting thrombus formation or they may act as a depot for sustained drug release.(ABSTRACT TRUNCATED AT 250 WORDS)
Pfliegler
G
G
Department of Biochemistry, Royal Free Hospital School of Medicine, Hampstead, London, UK.
el-Gamal
B
B
Badimon
J J
JJ
Badimon
L
L
Crawford
N
N
D000818:Animals; D001013:Aorta, Thoracic; D001792:Blood Platelets; D004339:Drug Compounding; D004547:Elastic Tissue / Q000473:pathology; D018274:Electroporation; D004730:Endothelium, Vascular / Q000293:injuries*; D016285:Iloprost / Q000008:administration & dosage* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013552:Swine / Q000097:blood; D013927:Thrombosis / Q000517:prevention & control*
D016285:Iloprost