Interactions of Liposomes and Platelets

 

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Summary

Rats were injected intravenously with liposomes of various compositions and sizes and blood platelet count measured. It was found that negatively-charged liposomal systems produced a transient reduction in platelet count in the first 5 minutes after injection which recovered by 60 minutes post-injection. This effect was most striking for multilamellar vesicles (MLV’s) containing phosphatidylglycerol (PG). Dose levels of 25 mg/kg of MLV’s containing 10 mole% PG caused the platelet count to drop from a control value of 1,086 ± 21 × 10⁹/1 to 193 ± 14 × 10⁹/1 by 2 minutes post-injection, an 82% decline. This thrombocytopenic effect was observed to diminish as vesicle size or vesicle dose was decreased. Positively-charged liposomes produced a less pronounced transient reduction in platelet count while neutral liposomes caused only a mild, transient platelet decline. This transient thrombocytopenic effect was not blocked by common anticoagulants and fibrinolytic agents but was pi evented by liposomal pretreatment. Radiolabeled platelet studies revealed that transient sequestration of platelets occurs in the liver and spleen 2 minutes after PG :EPC:CHOL MLV injection with a normalization of platelet distribution by 60 minutes post-injection. In vitro studies, using an automated blood counter suggest a transient association of liposomes and platelets occurring following injection. Liposomally-induced transient thrombocytopenia suggests a role for platelets in the biodistribution of liposomes.

• References

• 1 Ostro MJ. Liposomes: From Biophysics to Therapeutics. Marcel Dekker Inc New York: 1987
• 2 Ostro MJ, Cullis PR. Liposomes: Their use as intravenous pharmaceuticals. Am J Hosp Pharm 1988 (in press)
  PubMedGoogle Scholar
• 3 Storm G, Roerdink FH, Steerenberg PA, de Jong WH, Crommelin DJ A. Influence of lipid composition on the antitumour activity exerted by doxorubicin-containing liposomes in a rat solid tumour model. Cane Res 1987; 47: 3366-3372
  PubMedGoogle Scholar
• 4 Kim S, Kim DJ, Howell SB. Modulation of the peritoneal clearance of liposomal cytosine arabinoside by blank liposomes. Cane Res Pharm 1987; 19: 307-310
  PubMedGoogle Scholar
• 5 Sculier J-P, Coune A, Meunier F, Brassinne C, Laduran C, Hollart C, Collette N, Heymans C, Klastersky J. Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections. Eur J Cane Clin Oncol 1988; 24 (03) 527-538
  PubMedGoogle Scholar
• 6 Fountain MW, Dees C, Schultz RD. Enhanced intracellular killing of Staphylococcus aureus by canine monocytes treated with liposomes containing amikacin, gentamicin, kanamycin, and tobramycin. Curr Microbiol 1981; 6: 373-376
  CrossrefPubMedGoogle Scholar
• 7 Julian RL, Hsu MJ, Peterson D, Regen SD, Singh A. Short note: Interactions of conventional or photopolymerized liposomes with platelets in vitro. Exp Cell Res 1983; 146: 422-427
  CrossrefPubMedGoogle Scholar
• 8 Donald KJ, Tennent RJ. The relative roles of platelets and macrophages in clearing particles from the blood: the value of carbon particle clearance as a measure of reticuloendothelial phagocytosis. J Pathol 1975; 117: 235-245
  CrossrefPubMedGoogle Scholar
• 9 Schroit AJ. Synthesis and properties of a nonexchangeable radioiodi-nated phospholipid. Biochemistry 1982; 21: 5323-5328
  CrossrefPubMedGoogle Scholar
• 10 Mayer LD, Bally MB, Hope MJ, Cullis PR, Janoff AS. Solute distributions and trapping efficiencies observed in freeze-thawed multilamellar vesicles. Biochim Biophys Acta 1985; 817: 193-196
  CrossrefPubMedGoogle Scholar
• 11 Hope MJ, Bally MB, Webb G, Cullis PR. Production of large unilamellar vesicles by a rapid extrusion procedure. Biochim Biophys Acta 1985; 812: 55-65
  CrossrefPubMedGoogle Scholar
• 12 Mayer LD, Hope MJ, Cullis PR. Solute distribution and trapping efficiencies observed in freeze-thawed multilamellar vesicles. Biochim Biophys Acta 1986; 858: 161-168
  CrossrefPubMedGoogle Scholar
• 13 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
  CrossrefPubMedGoogle Scholar
• 14 “Student”. Metron 1925; V (03) 114-118
  PubMedGoogle Scholar
• 15 Brown CH, Bell WR, Shreiner DP. Effects of arvin on blood platelets. In vitro and in vivo studies. J Lab Clin Med 1972; 79 (05) 758-769
  PubMedGoogle Scholar
• 16 Plow EF, Ginsber MH, Marguerie GA. Expression and function of adhesive proteins on the platelet surface. In: The biochemistry of platelets Phillips DR, Shuman MA (eds). Academic Press Inc; Orlando, FL: 1986. pp 234-239
• 17 Gollub S, Ulin AW. Heparin-induced thrombocytopenia in man. J Lab Clin Med 1962; 59: 430-435
  PubMedGoogle Scholar
• 18 van Aken WG, Vreeken J. Accumulation of macromolecular particles in the reticuloendothelial system (RES) mediated by platelet aggregation and disaggregation. Thromb Diath Haemostas 1969; 22: 496-507
  PubMedGoogle Scholar
• 19 Villalobos TJ, Adelson E, Riley P. The effect of hypothermia on platelets and white cells in dogs. In: The physiology of induced hypothermia Dripps RD (ed). Nat Acad Sci Publ 451; Washington, DC: 1956. pp 186-188
• 20 Weissmann G, Korchak H, Finkelstein M, Smolen J, Hoffstein S. Uptake of enzyme-laden liposomes by animal cells in vitro and in vivo. Ann NY Acad Sci 1978; 308: 235-249
  CrossrefPubMedGoogle Scholar