Abstract
When unilamellar “stable” liposomes composed of a dialkyl analog of phosphatidylcholine, tetradecyloctadec-11-eno(1)phosphocholine (dialkyl-PC), plus cholesterol at 1∶1 molar ratio, and a trace of [3H]dialkyl-PC were injected into the vitreous of the rabbit eye, macrophage infiltration and phagocytosis of lipid were observed in retina including the epiretinal myelinated nerve fiber bundles, with no other neurotoxic effects. Little or no incorporation of [3H]dialkyl-PC was observed in the distal tissues of the optic system. With “labile” vesicles composed of egg lecithin, trace amounts of [3H]dialkyl-PC, and phosphatidic acid, no morphological changes occurred. After a lag of more than 7 days [3H]dialkyl-PC appeared in superior colliculus, indicating axonal transport of the lipid in an anterograde direction. Experiments with submandibular and parotid gland indicated retrograde transport of the lipid. The data do not suggest axonal transport of intact (stable) liposomes, but suggest that intact phospholipid molecules can be axonally transported.
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References
Gregoriades, G. 1976. The carrier potential of liposomes in biology and medicine. N. Engl. J. Med. 295:704–710.
Weissman, G., Cohen, C., andHoffstein, S. 1977. Introduction of enzymes by means of liposomes into non-phagocytic human cells in vitro. Biochim. Biophys. Acta 498:375–385.
Cohen, C. M., Weissmann, G., Huffstein, S., Awasthi, Y. C., andSrivastava, S. K. 1976. Introduction of purified hexosaminidase A into Tay-Sachs leukocytes by means of immunoglobulin-coated liposomes. Biochemistry 15:452–460.
Weissmann, G., Zurier, R. B., Speiler, P. J., andGoldstein, I. M. 1971. Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles. J. Exp. Med. 134:149s-165s.
Bruni, A., Toffano, G., Leon, A., andBorato, E. 1976. Pharmacological effects of phosphatidylserine liposomes. Nature 260:331–333.
Deshmukh, D. S., Bear, W. D., Wisniewski, H. M., andBrockerhoff, H. 1978. Long-living liposomes as drug carriers. Biochem. Biophys. Res. Commun. 82:328–334.
Fong, J. W., Tirri, L. J., Deshmukh, D. S., andBrockerhoff, H. 1977. Studies on hydrogen belts of membranes: I. Diester, diether and dialkyl phosphatidylcholines and polyoxy ethylene glycerides in monolayers with cholesterol. Lipid 12:857–862.
Tirri, L. J., Schmidt, P. C., Pullarkat, R. K., andBrockerhoff, H. 1977. Studies on hydrogen belt of membranes: II. Non-electrolyte permeability of liposomes of diester, diether, and dialkyl phosphatidylcholine and cholesterol. Lipids 12:863–868.
Kates, M. 1973. Techniques of Lipidology, North Holland Publishing Co., Amsterdam.
Adams, D. H., Joyce, G., Richardson, V. J., Ryman, B. E., andWisniewski, H. M. 1977. Liposome toxicity in the mouse central nervous system. J. Neurol. Sci. 31:173–179.
Kristensson, K., andWisniewski, H. M. 1976. Penetration of protein tracers into the epiretinal portion of the optic nerve in the rabbit eye. J. Neurol. Sci. 30:411–416.
Brockerhoff, H., Wisniewski, H. M., Lipton, L. C., andDeshmukh, D. S. 1980. Retention of dialkylphosphatidylcholine in myelin and other membranes. Neurochem. Res. 5:619–630.
Haley, J. E., Tirri, L. J., andLedeen, R. W. 1979. Axonal transport of lipids in the rabbit optic system. J. Neurochem. 32:727–734.
Toews, A. D., Goodrum, J. F., andLorell, P. 1979. Axonal transport of phospholipids in rat visual system. J. Neurochem. 32:1165–1173.
Grafstein, B., Miller, J. A., Ledeen, R. W., Haley, J., andSpecht, S. C. 1975. Axonal transport of phospholipid in goldfish optic system. Exp. Neurol. 46:261–281.
Currie, J. R., Grafstein, B., Whitnall, M. H., andAlpert, R. 1978. Axonal tranpport of lipid in goldfish optic axon. Neurochem. Res. 3:479–492.
Kristensson, K. 1978. Retrograde transport of macromolecules in axons. Rev. Pharmacol. Toxicol. 18:97–110.
Stoeckel, K., Schwab, M., andThoenen, H. 1977. Role of gangliosides in the uptake and retrograde axonal transport of cholera and tetanus toxin as compared to nerve growth factor and wheat germ agglutinin. Brain Res. 132:273–285.
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Deshmukh, D.S., Kristensson, K., Wisniewski, H.M. et al. Toxicity and neuronal transport of stable liposomes and phospholipid in the nervous system. Neurochem Res 6, 143–151 (1981). https://doi.org/10.1007/BF00964831
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DOI: https://doi.org/10.1007/BF00964831