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  • Title: Acute toxicity and depression of phagocytosis in vivo by liposomes: influence of lysophosphatidylcholine.
    Author: Lutz J, Augustin AJ, Jäger LJ, Bachmann D, Brandl M.
    Journal: Life Sci; 1995; 56(2):99-106. PubMed ID: 7823764.
    Abstract:
    Small unilamellar phospholipid vesicles (liposomes), intended as drug carriers, have recently been demonstrated to reversibly depress phagocytic activity in rats when injected in a single high dose (2g of lipid per kg body weight) as revealed by the carbon clearance test. Depression of the phagocytic function was found to vary widely depending on the lipid used [M. Brandl et al., Pharm. Pharmacol. Lett., 4 (1) 1-4, 1994]. This study has now been extended in two directions: Firstly, liposomes made of the same type of lipid but different batches of raw material were compared in terms of their influence on phagocytosis as well as for their contents of impurities. The test revealed great variability of RES suppression between different batches of hydrogenated soy PC, whereas the reproducibility of the carbon clearance test was satisfactory with liposomes made of a single batch of raw material. Thin layer chromatographic analyses of the used phosphatidylcholines (PCs) and limulus tests on lipopolysaccharides revealed lysophosphatidylcholine (lysoPC) as the only impurity which showed parallels with the observed differences in phagocytosis. Secondly by "spiking" phosphatidylcholine with increasing amounts of lysoPC the latter could be proven to enhance RES depression by liposomes in a dose-dependent manner. At the same time a strong and dose-limiting increase in acute toxicity of PC vesicles was observed with increasing contents of lysoPC. However, in cholesterol-containing vesicles lysoPC-spiking did not significantly alter their behaviour, for lysoPC contents of up to 10%. Only PC/cholesterol-vesicles containing lysoPC contents as high as 15% provoked enhanced RES depression and toxicity compared to lysoPC-free vesicles. LysoPC and cholesterol in liposomes are known to play a destabilizing and stabilizing role respectively within liposomal bilayers which might influence recognition and uptake of vesicles by macrophages and thus modulation of phagocytosis.
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