RETENTION OF CYTOSINE-ARABINOSIDE IN MOUSE LUNG FOLLOWING INTRAVENOUS ADMINISTRATION IN LIPOSOMES OF DIFFERENT SIZE

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (3) , 124-128
Abstract
An extrusion technique obtained multilamellar lipid vesicles (MLV, liposomes) of different size distribution. The larger MLV ranged in diameter from 0.1-2.6 .mu. and the smaller from 0.1-1.5 .mu., and were composed of phosphatidylserine/phosphatidylcholine/cholesterol in the molar ratio 1:4:5. After i.v. injection of large and small MLV containing encapsulated [3H]cytosine arabinoside (ara-C) [an antineoplastic drug], their distribution in various organs showed that the fraction of the dose associated with lung was greater for large MLV relative to small MLV by factors of 3.6-10 after 1 h, 5.3-14 after 4 h and 17-23 after 24 h. For large MLV more than 50% of drug remaining in vivo after 24 h was associated with the lung, compared with 2.5% for small MLV. Almost all of the 3H associated with lung at all times for both large and small MLV could be accounted for by unchanged ara-C. Differences in 3H levels between small and large MLV in other tissues were much less dramatic or were not significant. The apparent in vivo stability of the liposomes was not affected by size. The data are consistent with an initial trapping of large MLV during 1st passage in the lung, with subsequent binding and retention. Release of ara-C from large or small MLV in the lung is apparently slow relative to metabolism.