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  • Title: Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems.
    Author: Adrian JE, Poelstra K, Scherphof GL, Molema G, Meijer DK, Reker-Smit C, Morselt HW, Kamps JA.
    Journal: J Hepatol; 2006 Mar; 44(3):560-7. PubMed ID: 16368158.
    Abstract:
    BACKGROUND/AIMS: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied. METHODS: M6P-HSA was covalently coupled to the liposomal surface and the uptake and binding of 3H-labelled M6P-HSA liposomes by primary rat HSC and liver endothelial cells was determined. The targeting ability of M6P-HSA liposomes to HSC was tested in bile duct ligated rats using immunohistochemical methods. RESULTS: The association of M6P-HSA liposomes with HSC was 4-fold higher than of control liposomes. An excess of M6P-HSA inhibited this association by 58%, indicating M6P receptor specificity. The scavenger receptor competitor polyinosinic acid abolished association of M6P-HSA liposomes with HSC. M6P-HSA liposomes also amply associated with endothelial cells, which abundantly express scavenger receptors. Endocytosis of M6P-HSA liposomes by HSC was temperature dependent and could be inhibited by monensin. In the fibrotic liver M6P-HSA liposomes co-localised with HSC. CONCLUSIONS: Coupling of M6P-HSA to liposomes strongly increases the in vitro uptake of these liposomes by HSC and endothelial cells. Both the mannose 6-phosphate receptor and the scavenger receptors are involved in the uptake process. M6P-HSA liposomes are potential drug carriers to HSC in the fibrotic liver.
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