Summary
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. This platelet drug delivery strategy may have application
in the prevention of the thrombotic and reste-notic events that can occur post angioplasty,
or following therapy with thrombolytics, or after more invasive surgical procedures
involving vascular reconstruction or prosthetic implantation.
