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. 1996 Jan;40(1):225–229. doi: 10.1128/aac.40.1.225

Comparative pharmacokinetics, distributions in tissue, and interactions with blood proteins of conventional and sterically stabilized liposomes containing 2',3'-dideoxyinosine.

P Harvie 1, A Désormeaux 1, M C Bergeron 1, M Tremblay 1, D Beauchamp 1, L Poulin 1, M G Bergeron 1
PMCID: PMC163088  PMID: 8787911

Abstract

The pharmacokinetics and distribution in tissue of 2',3'-dideoxyinosine (ddI) encapsulated in sterically stabilized liposomes have been evaluated in rats. Most of the sterically stabilized liposomes concentrated in the spleen with a peak level at 24 h after their intravenous injection. An extended half-life in plasma was observed for sterically stabilized liposomes (14.5 h) compared with that of conventional liposomes (3.9 h). The systemic clearance of ddI incorporated in sterically stabilized liposomes was 180 times lower than that of the free drug. The levels of in vitro and in vivo protein binding on both conventional and sterically stabilized liposomes were also evaluated. Results suggest that the amount of proteins associated with liposomes might not be the only factor involved in the in vivo clearance of liposomes, as this process may also be influenced by the nature of the bound blood proteins.

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Selected References

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  1. Allen T. M. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol Sci. 1994 Jul;15(7):215–220. doi: 10.1016/0165-6147(94)90314-x. [DOI] [PubMed] [Google Scholar]
  2. Chonn A., Semple S. C., Cullis P. R. Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. J Biol Chem. 1992 Sep 15;267(26):18759–18765. [PubMed] [Google Scholar]
  3. Connolly K. J., Hammer S. M. Antiretroviral therapy: reverse transcriptase inhibition. Antimicrob Agents Chemother. 1992 Feb;36(2):245–254. doi: 10.1128/aac.36.2.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. De Clercq E. HIV inhibitors targeted at the reverse transcriptase. AIDS Res Hum Retroviruses. 1992 Feb;8(2):119–134. doi: 10.1089/aid.1992.8.119. [DOI] [PubMed] [Google Scholar]
  5. Devine D. V., Wong K., Serrano K., Chonn A., Cullis P. R. Liposome-complement interactions in rat serum: implications for liposome survival studies. Biochim Biophys Acta. 1994 Apr 20;1191(1):43–51. doi: 10.1016/0005-2736(94)90231-3. [DOI] [PubMed] [Google Scholar]
  6. Désormeaux A., Harvie P., Perron S., Makabi-Panzu B., Beauchamp D., Tremblay M., Poulin L., Bergeron M. G. Antiviral efficacy, intracellular uptake and pharmacokinetics of free and liposome-encapsulated 2',3'-dideoxyinosine. AIDS. 1994 Nov;8(11):1545–1553. doi: 10.1097/00002030-199411000-00005. [DOI] [PubMed] [Google Scholar]
  7. Faulds D., Brogden R. N. Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. Drugs. 1992 Jul;44(1):94–116. doi: 10.2165/00003495-199244010-00008. [DOI] [PubMed] [Google Scholar]
  8. Gabizon A., Papahadjopoulos D. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6949–6953. doi: 10.1073/pnas.85.18.6949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
  10. Gregoriadis G. Overview of liposomes. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):39–48. doi: 10.1093/jac/28.suppl_b.39. [DOI] [PubMed] [Google Scholar]
  11. Harvie P., Désormeaux A., Gagné N., Tremblay M., Poulin L., Beauchamp D., Bergeron M. G. Lymphoid tissues targeting of liposome-encapsulated 2',3'-dideoxyinosine. AIDS. 1995 Jul;9(7):701–707. doi: 10.1097/00002030-199507000-00006. [DOI] [PubMed] [Google Scholar]
  12. Klibanov A. L., Maruyama K., Torchilin V. P., Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990 Jul 30;268(1):235–237. doi: 10.1016/0014-5793(90)81016-h. [DOI] [PubMed] [Google Scholar]
  13. Lasic D. D., Martin F. J., Gabizon A., Huang S. K., Papahadjopoulos D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta. 1991 Nov 18;1070(1):187–192. doi: 10.1016/0005-2736(91)90162-2. [DOI] [PubMed] [Google Scholar]
  14. Loughrey H. C., Bally M. B., Reinish L. W., Cullis P. R. The binding of phosphatidylglycerol liposomes to rat platelets is mediated by complement. Thromb Haemost. 1990 Aug 13;64(1):172–176. [PubMed] [Google Scholar]
  15. Meltzer M. S., Skillman D. R., Gomatos P. J., Kalter D. C., Gendelman H. E. Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol. 1990;8:169–194. doi: 10.1146/annurev.iy.08.040190.001125. [DOI] [PubMed] [Google Scholar]
  16. Mitsuya H., Jarrett R. F., Matsukura M., Di Marzo Veronese F., DeVico A. L., Sarngadharan M. G., Johns D. G., Reitz M. S., Broder S. Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2033–2037. doi: 10.1073/pnas.84.7.2033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nordback I. H., Olson J. L., Chaisson R. E., Cameron J. L. Acute effects of a nucleoside analog dideoxyinosine (DDI) on the pancreas. J Surg Res. 1992 Dec;53(6):610–614. doi: 10.1016/0022-4804(92)90262-x. [DOI] [PubMed] [Google Scholar]
  18. Patel H. M. Serum opsonins and liposomes: their interaction and opsonophagocytosis. Crit Rev Ther Drug Carrier Syst. 1992;9(1):39–90. [PubMed] [Google Scholar]
  19. Rahman Y. E., Cerny E. A., Patel K. R., Lau E. H., Wright B. J. Differential uptake of liposomes varying in size and lipid composition by parenchymal and kupffer cells of mouse liver. Life Sci. 1982 Nov 8;31(19):2061–2071. doi: 10.1016/0024-3205(82)90098-4. [DOI] [PubMed] [Google Scholar]
  20. Ray G. F., Mason W. D., Badr M. Z. Pharmacokinetics of the anti-AIDS drug 2',3'-dideoxyinosine in the rat. Drug Metab Dispos. 1990 Sep-Oct;18(5):654–658. [PubMed] [Google Scholar]
  21. Roerdink F., Dijkstra J., Hartman G., Bolscher B., Scherphof G. The involvement of parenchymal, Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes. Effects of lanthanum and gadolinium salts. Biochim Biophys Acta. 1981 Sep 18;677(1):79–89. doi: 10.1016/0304-4165(81)90148-3. [DOI] [PubMed] [Google Scholar]
  22. Senior J. H. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst. 1987;3(2):123–193. [PubMed] [Google Scholar]
  23. Shelton M. J., O'Donnell A. M., Morse G. D. Didanosine. Ann Pharmacother. 1992 May;26(5):660–670. doi: 10.1177/106002809202600511. [DOI] [PubMed] [Google Scholar]
  24. Woodle M. C., Lasic D. D. Sterically stabilized liposomes. Biochim Biophys Acta. 1992 Aug 14;1113(2):171–199. doi: 10.1016/0304-4157(92)90038-c. [DOI] [PubMed] [Google Scholar]
  25. Woodle M. C. Surface-modified liposomes: assessment and characterization for increased stability and prolonged blood circulation. Chem Phys Lipids. 1993 Sep;64(1-3):249–262. doi: 10.1016/0009-3084(93)90069-f. [DOI] [PubMed] [Google Scholar]
  26. Yarchoan R., Pluda J. M., Thomas R. V., Mitsuya H., Brouwers P., Wyvill K. M., Hartman N., Johns D. G., Broder S. Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS-related complex. Lancet. 1990 Sep 1;336(8714):526–529. doi: 10.1016/0140-6736(90)92085-v. [DOI] [PubMed] [Google Scholar]

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