Abstract
Human serum albumin (HSA) derivatized with cis -aconitic anhydride was covalently coupled to liposomes with a size of approximately 100 nm [polyaconitylated HSA (Aco-HSA) liposomes]. Within 30 min after injection into a rat, Aco-HSA liposomes were completely cleared from the blood and almost exclusively taken up by the liver, whereas in control liposomes 80% was still present in the blood at that time. Endothelial cells were shown to account for almost two-thirds of the hepatic uptake of the Aco-HSA liposomes, the remainder being recovered mainly in the liver macrophages (Kupffer cells). With fluorescently labeled liposomes it was shown that the Aco-HSA liposomes target a vast majority (>85%) of the cells in the endothelial cell population. Control liposomes were not taken up to a significant extent by the endothelial cells. Uptake of Aco-HSA liposomes by both endothelial and Kupffer cells was inhibited by preinjection with polyinosinic acid, indicating the involvement of scavenger receptors in the uptake process. The uptake of Aco-HSA liposomes by liver endothelial cells was dependent on liposome size; with increasing liposome diameter endothelial cell uptake decreased in favor of Kupffer cell uptake. We have demonstrated that massive in vivo targeting of liposomes to a defined cell population other than macrophages is possible. Aco-HSA liposomes thus may represent an attractive drug carrier system for treatment of various liver or liver endothelium-associated disorders.
References
33
Referenced
110
- A R Thierry, A Rahman, A Dritschilo Gene Regulation: Biology of Antisense RNA and DNAR P Erickson, J G Izant, eds R P Erickson, J G Izant (Raven, New York), pp. 147–161 (1992). / Gene Regulation: Biology of Antisense RNA and DNA by Thierry A R (1992)
10.1016/0169-409X(96)00002-6
10.3109/10611869509059214
10.1016/0005-2736(95)00268-5
10.1016/0165-6147(94)90314-X
10.1007/BF00686828
10.1126/science.275.5299.547
- R W Jansen, D Schols, R Pauwels, E De Clercq, D K F Meijer Mol Pharmacol 44, 1003–1007 (1993). / Mol Pharmacol by Jansen R W (1993)
10.1016/0005-2736(95)00218-9
10.1016/S0021-9258(18)52241-9
10.1016/S0006-291X(05)81249-5
10.1016/S0021-9258(19)52451-6
10.1016/0003-2670(61)80041-X
- M K Bijsterbosch, G J Ziere, Th J C Van Berkel Mol Pharmacol 36, 484–489 (1989). / Mol Pharmacol by Bijsterbosch M K (1989)
- T Daemen, A Veninga, F H Roerdink, G L Scherphof Cancer Res 46, 4330–4335 (1986). / Cancer Res by Daemen T (1986)
10.1016/0014-5793(86)80607-X
10.1016/S0169-409X(96)00457-7
10.1016/S0021-9258(17)44160-3
10.1016/0304-4165(81)90148-3
10.3109/08982109409037038
10.1016/0005-2736(86)90262-2
10.1016/0304-4165(79)90361-1
10.1016/0005-2736(95)00183-2
10.1146/annurev.bi.63.070194.003125
10.1161/01.ATV.12.9.1079
10.1182/blood.V63.2.270.270
- J A A M Kamps, H W M Morselt, G L Scherphof Prog Drug Delivery Syst 5, 89–92 (1996). / Prog Drug Delivery Syst by Kamps J A A M (1996)
10.1002/hep.1840180310
10.1016/0168-8278(92)90042-N
10.1055/s-2007-1007278
10.1016/S0168-8278(05)80579-3
10.1097/00002030-199406000-00004
10.1016/0166-3542(92)90058-D
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:31 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 2:22 p.m.) |
Indexed | 1 month ago (Aug. 2, 2025, 12:50 a.m.) |
Issued | 27 years, 10 months ago (Oct. 14, 1997) |
Published | 27 years, 10 months ago (Oct. 14, 1997) |
Published Online | 27 years, 10 months ago (Oct. 14, 1997) |
Published Print | 27 years, 10 months ago (Oct. 14, 1997) |
@article{Kamps_1997, title={Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.21.11681}, DOI={10.1073/pnas.94.21.11681}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kamps, Jan A. A. M. and Morselt, Henriëtte W. M. and Swart, Pieter J. and Meijer, Dick K. F. and Scherphof, Gerrit L.}, year={1997}, month=oct, pages={11681–11685} }