Encapsulation of carbacyclin within human platelets and its effect on platelet aggregation in vitro

In the course of exploring the use of platelets as carrier vehicles for drug delivery in vivo, some initial studies are reported on the effect of platelet encapsulated anti-platelet drug on platelet aggregation in vitro. A possible clinical application may be in directing drug loaded cells to areas of vascular damage during balloon angioplasty, to reduce over-excessive recruitment of platelets to the injury site by the slow release of the drug from a lesion-adherent drug-loaded platelets and minimise the risk of thrombotic re-occulsion and restenosis. The stable prostacyclin analogue, carbacyclin, has been encapsulated within reversibly electroporated human platelets using high voltage discharges [1,2]. During electroporation, the drug diffuses to equilibrium across the platelet membrane pores reaching intracellular concentration of 55.2 +/- 2.8% [mean +/- SD, n=6] of the concentration, to which the cells were exposed. Leakage rates for the drug from washed platelets stored at room temperature were maximum after about 2 days, being 40% and 51% for loading concentrations of 100 micro g/ml and 200 micro g/ml, respectively, with little further losses at 5 days. In aggregometry, 1:1 mixture of autologous platelets loaded with carbacyclin [at loading concentration of 200 micro g/ml] and control [sham-encapsulated] platelets inhibited agonist-induced platelet aggregation by 50%. Biological assays of the entrapped carbacyclin showed that the drug's functional integrity [i.e. the ability to inhibit platelet aggregation] is unimpaired within the platelet cytosol. These data suggest that platelet encapsulated carbacyclin may be used as suitable anti-platelet agent for further studies in vivo, which when trageted to injured blood vessels may prevent over-excessive recruitment of platelets to the injury site and reduce thrombotic events

Removal of sialic acid from reversibly electroporated rat platelets: effect on platelet survival and potential use as carrier vehicles for drug delivery in vivo

In the course of exploring the use of blood platelets as carrier vehicles for drug delivery to specific sites in vivo, some initial studies are reported on the effect of removing sialic acid from the surface of reversibly electroporated rat platelets, on the in vivo platelet survival. Treatment of platelets with neuraminidase for 60 min led to a maximum removal of platelet surface sialic acid which represented 45% of the platelet total sialic acid content. Neuraminidase - treated platelets which have been reversibly electroporated using a high voltage discharge pulses [1,2], labelled with 111 indium oxine and reinfused into rats, were rapidly removed from the circulation [after 2 hr] and the majority of radioactivity was found in the liver [76%], followed by lungs [4%] and spleen [1.6%]. It has been suggested that electroporated/resealed platelets lacking sialic acid on their surface as a result of neuraminidase treatment are recognised as 'foreign" and are rapidly taken out of the circulation by tile reticulo-endothelial system, primarily in the liver. These data suggest that electroporated/ resealed platelets lacking sialic acid on their membrane may be used as vehicles for the direct delivery of drugs and other agents to the liver in various situations. Possible clinical applications may be to deliver macrophage-activating drugs to the liver to fight and kill the cancer cells and cytotoxic drugs to secondary tumors in the liver

Effect of triazine derivatives on carbohydrate metabolism in rats

Because of the increasing interest in the therapeutic use of triazine derivatives, the effect of 3-hydrazino-5, 6-diphenyl [1, 2, 4]triazine [Triazine I] and 3-hydrazino [1, 2, 4] triazine [5, 6-b] indole [Triazine II] on some parameters of carbohydrate metabolism, were studied in rats. In rats treated with either of the two triazines, serum glucose rose significantly, serum insulin level was significantly reduced, serum lactic dehydrogenase [LDH] activity increased significantly, whereas, serum cirate and muscle glycogen did not change significantly. Liver glycogen content was significantly reduced with triazine I and did not change with triazine II. On the other hand, blood pyruvate level did not change significantly with triazine I, whereas triazine II reduced it. These results suggest that triazine derivatives may interfere with carbohydrate metabolism in rats