Platelet Distribution in Rabbits Following lnfusion of Liposomes

Summary

This investigation determined the organ distribution of liposomes containing egg phosphatidylcholine and cholesterol with egg phosphatidylglycerol (PG liposomes) or without (PC liposomes) and the effect of each liposome on platelet distribution in rabbits. Eight minutes after⁵¹ chromium-labelled platelets were given intravenously, either saline (n = 7), iodinated PG liposomes (n = 5) or iodinated PC liposomes (n = 5) were infused. T\ro minutes later the organ distribution of ⁵¹Cr-platelets and ¹²⁵I-liposomes were compared. The PG liposomes produced a 41λ5% reduction in circulating platelet counts while PC liposomes did not. The PG liposomes decreased circulating ⁵¹Cr-platelets by a factor of 2 and increased platelet recoveries in the liver and lungs. The increased platelet recovery in the liver was associated with a greater PG liposome recovery. When animals receiving PG liposomes were studied over 60 minutes, both the labelled and unlabelled platelet counts returned to control values by 30 minutes and the ⁵¹Cr-platelet distribution between organs was similar to control values. These data indicate that platelets and PG liposomes initially sequester together and that this plateletliposome interaction is specific for PG liposomes. However, the platelet sequestration is transient and by 60 minutes the platelets were released and circulating.

Keywords

Platelets - Liposomes - Platelet-endothelial interactions - Liposome biodistribution - Radiolabelled platelet kinetics - Platelet-liposome interactions

• References

• 1 Lopez-Berestein G, Fainstein V, Hopfer R, Mehta K, Sullivan M, Keating M, Rosenblum MG, Mehta R, Luna M, Hersh EM, Reuben J, Juliano RL, Bodey GP. Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study. J Inf Dis 1985; 151: 704-710
• 2 Sells RA, Owen RR, New RR C, Gilmore IT. Reduction in toxicity of doxorubicin by liposomal entrapment. Lancet 1987; 2 (8559) 624-626
• 3 Alving CR, Steck EA, Chapman Jr WL, Waits VB, Hendricks LD, Swartz GM, Hanson WL. Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs. Proc Natl Acad Sci USA 1987; 75: 2959-2963
• 4 Saiki I, Milas L, Hunter N, Fidler IJ. Treatment of experimental lung metastasis with local thoracic irradiation followed by systemic macrophage activation with liposomes containing muramyl tripeptidc. Cancer Res 1986; 46: 4966-4970
• 5 Tanswell AK, Freeman BA. Liposome-entrapped antioxidant enzymes prevent lethal O₂ toxicity in the newborn rat. J Appl Physiol 1987; 63: 347-352
• 6 Dapergolas G, Neerunjun ED, Gregoriadis G. Penetration of target areas in the rat by liposome-associated bleomycin, glucose oxidase and insulin. FEBS Lett 1976; 63: 235-239
• 7 Weinstein JN, Magin RL, Cysyk RL, Zaharko DS. Treatment of solid L1210 murine tumors with local hyperthermia and temperature- sensitive liposomes containing methotrexate. Cancer Res 1980; 40: 1388-1395
• 8 Saunders RM, Alexander JJ. The use of liposomes to study drug- membrane interactions. S Afr Med J 1986; 69: 103-106
• 9 Reinish LW, Bally MB, Larghery HC, Cullis PR. The effect of liposomes on platelet count in vivo. Thromb Haemostas, in press.
• 10 Gutkowski RF, Dworkin HJ. Kit produced ^99mTc-labelled red blood cells for spleen imaging. J Nucl Med 1974; 15: 1187-1191
• 11 Schroit AJ. Synthesis and properties of a nonexchangeable radioiodinated phospholipid. Biochemistry 1982; 21: 5323-5328
• 12 Mayer LD, Hope MJ, Cullis PR, Janoff AS. Solute distributions and trapping efficiencies observed in freeze-thawed mutilamellar vesicles. Biochim Biophys Acta 1985; 817: 193-196
• 13 Hogg JC, Martin BA, McClean T. Regional differences in erythrocyte transit in normal lungs. J Appl Physiol 1985; 59: 1266-1271
• 14 Doerschuk CM, Allard MF, Martin BA, MacKenzie A, Autor AA, Hogg JC. Marginated pool of neutrophils in rabbit lungs. J Appl Physiol 1987; 63: 1806-1815
• 15 Bonte F, Juliano RL. Interactions of liposomes with serum proteins. Chem Phys Lipids 1986; 40: 359-372
• 16 Senior J, Crawley JC W, Gregoriadis G. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim Biophys Acta 1985; 839: 1-8
• 17 Dijkstra J, van Galen M, Scherphof G. Influence of liposome charge on the association of liposomes with Kupffer cells in vitro. Effects of divalent cations and competition with latex particles. Biochim Biophys Acta 1985; 813: 287-297
• 18 Nicholas AR, Jones MN. The absorption of phospholipid vesicles by perfused rat liver depends on vesicle surface charge. Biochim Biophys Acta 1986; 860: 600-607