Abstract
[3H] Adenosine-3′,5′-cyclic monophosphate (cAMP) could be entrapped efficiently into small unilamellar vesicles when bound to cAMP-dependent protein kinase. The leakage of [3H]cAMP protein kinase complex from liposomes was reduced by more than 60% as compared to free [3H]cAMP. Hyperosmolar mannitol increased the delivery of liposomally entrapped [3H]cAMP protein kinase to the brain with maximum uptake occurring at 10 min after mannitol administration. Optimal delivery to the brain was observed when vesicles composed of total brain lipids or phosphatidylcholine:cholesterol:sulfatides (7:2:1) were used. A slower clearance of liposomally entrapped material from brain tissue was seen under hyperosmolar conditions.
Similar content being viewed by others
references
Naoi, M. and Yagi, K. 1980. Incorporation of enzyme through blood-brain barrier into the brain by means of liposomes. Biochem. Int. 1:591–596.
Yagi, K., Naoi, M., Sakai, H., Abe, H., Konishi, H., and Arichi, S. 1982. Incorporation of enzyme into the brain by means of liposomes of novel composition. J. Appl. Biochem. 4:121–125.
Umezawa, F. and Eto, Y. 1988. Liposome targeting to mouse brain: Mannose as a recognition marker. Biochem. Biophys. Res. Commun. 153:1038–1044.
Kobayashi, K., Han, M., Watarai, S, and Yasuda, T. 1996. Availability of liposomes as drug carriers to the brain. Acta Med. Okayama 50:67–72.
Kakinuma, K., Tanaka, R., Takahashi, H., Watanabe, M., Nakagawa, T., and Kuroki, M. 1996. J. Neurosurg. 84:180–184.
Fredericks, W. R. and Rapoport, S. I. 1988. Reversible osmotic opening of blood-brain barrier in mice. Stroke 19:266–268.
Hasegawa, H. Allen, J. C., Mehta, B. M., Shapiro, W. R., and Posner, J. B. 1979. Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol in carcinomatous meningitis. Neurology 29:1280–1286.
Neuwelt, E. A., Pagel, M. A., and Dix, R. D. 1991. Delivery of ultraviolet-inactivated <sup>35</sup>S-herpes virus across an osmotically modified blood-brain barrier. J. Neurosurg. 74:475–479.
Gulati, A., Agarwal, S. K., Shukla, R., Srimal, R. C., and Dhawan, B. N. 1985. The mechanism of opening of the blood-brain barrier by hypertonic saline. Neuropharmacology 24:909–913.
Norman, A. B., Bertram, K. J., Thomas, S. R., Pratt, R. G., Samaratunga, R. C., and Sanberg, P. R. 1991. Magnetic resonance imaging of rat brain following in vivo disruption of the cerebral vasculature. Brain Res. Bull. 26:593–597.
Preparation of liposomes. Pages 45–46, in New, R. R. C. (ed.), Liposomes: A Practical Approach 1990. IRL Press, Oxford University Press, New York.
McClare, C. W. F. 1971. An accurate and convenient organic phosphorous assay. Anal. Biochem. 39:527.
Frokjaer, S., Hjorth, E. L., and Worts, O. 1986. Stability testing of liposomes during storage. Pages 238–239, in Gregoriadis, G. (ed.), Liposome Technology, Vol. 1, CRC Press, Boca Raton, Fla.
Folch, J., Lees, M., and Sloane-Stanley, G. H. 1957. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226:497–509.
Tyrell, D. A., Richardson, V. J., and Ryman, B. E. 1977. The effect of serum protein fractions on liposome-cell interaction in cultured cells and the perfused rat liver. Biochem. Biophys. Acta 497:469–480.
Naoi, M. and Yagi, K. 1984. Effect of glycolipids contained in liposomes on the incorporation of β-galactosidase into specific organs. Biochem. Int. 9:267–272.
Kato, K., Yoshida, J., Kageyama, N., Kojima, N., and Yagi, K. 1988. Liposome-entrapped human interferon-β: Its pharmacokinetics and antitumor activity against human brain tumor cells. J. Clin. Biochem. Nutr. 4:139–147.
Gennuso, R., Spigelman, M. K., Chinol, M., Zappulla, R. A., Nieves, J., Vallabhajosula, S., Alberto-Paciucci, P., Goldsmith, S. J., and Holland, J. F. 1993. Effect of blood-brain barrier and blood-tumor barrier modification on central nervous system liposomal uptake. Cancer Invest. 11:118–128.
Sakamoto, A. and Ido, T. 1993. Liposome targeting to rat brain: Effect of osmotic opening of the blood-brain barrier. Brain Res. 629:171–175.
Lesage, D., Cao, A., Briane, D., Lievere, N., Coudert, R., Raphael, M., Salzmann, J., and Taillandier, E. 2002. Evaluation and optimization of DNA delivery into glioblastoma 9L cells by a cholesterol-based cationic liposome. Biochim. Biophys. Acta 1564:393–302.
Geisert, E. E. Jr., Del-Mar, N. A., Owens, J. I., and Holmberg, E. G. 1995. Transfecting neurons and glia in the rat using pH-sensitive immunoliposomes. Neurosci. Lett. 184,40–43.
Iwamoto, Y., Yang, K., Clifton, G. L., and Hayes, R. L. 1995. Liposome mediated BDNF cDNA transfer in intact and injured rat brain. Neuroreport 7:609–612.
Cao, Y. J., Shibata, T., and Rainov, N. G., 2002. Liposome-mediated transfer of the bcl-2 gene resulted in neuroprotection after in-vivo transient focal cerebral ischemia in an animal model. Gene Therap. 9:415–419.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gomes, I., Sharma, S.K. Uptake of Liposomally Entrapped Adenosine-3′-5′-Cyclic Monophosphate in Mouse Brain. Neurochem Res 29, 441–446 (2004). https://doi.org/10.1023/B:NERE.0000013749.65266.a2
Issue Date:
DOI: https://doi.org/10.1023/B:NERE.0000013749.65266.a2