Liposomes endothelial cells

Fig. 26 MR images of tumors of mice after they were injected with (a) paramagnetic av[33-specific RGD-liposomes and (b) nonspecific paramagnetic RAD-liposomes. (c, d) Fluorescence microscopy of 10 pm sections from dissected tumors revealed a distinct difference between tumors of mice that were injected with RGD-liposomes (c) or RAD-liposomes (d). Vessel staining was done with an endothelial cell-specific FITC-CD31 antibody. The red fluorescence represents the liposomes and the green fluorescence represents blood vessels. RGD-liposomes were exclusively found within the vessel lumen or associated with vessel endothelial cells (c), whereas RAD-liposomes (d) were also found outside blood vessels within the tumor (Adapted from [88])...

Sauer I, et al. An apolipoprotein E-derived peptide mediates uptake of sterically stabilized liposomes into brain capillary endothelial cells. Biochemistry 2005 44 2021. 

Spragg, D.D., D.R. Alford, R. Greferath, C.E. Larsen, K.D. Lee, G.C. Gurtner, M.I. Cybulsky, PE Tosi, C. Nicolau, and M.A. Gimbrone, Jr., Immunotargeting of liposomes to activated vascular endothelial cells a strategy for site-selective delivery in the cardiovascular system. Proc Natl Acad Sci USA, 1997. 94(16) 8795-800. 

Thole, M., et al. 2002. Uptake of cationized albumin coupled liposomes by cultured porcine brain microvessel endothelial cells and intact brain capillaries. J Drug Target 10 337. 

Gosk, S., et al. 2004. Targeting anti-transferrin receptor antibody (0X26) and OX26-conjugated liposomes to brain capillary endothelial cells using in situ perfusion. J Cereb Blood Flow Metab 24 1193. 

J. A. A. M. Kamps, H. W. M. Morselt, P. J. Swart, D. K. F. Meijer, and G. L. Scherphof, Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells, Proc. Natl. Acad. Sci. USA 94 11681-11685, (1997). 

Moreover, Voinea et al. attached antibodies against vascular cell adhesion molecule-1 (VCAM-1) overexpressed on activated human endothelial cells on liposomes with the intention of using them as drug carriers [162], A-gluraryl-PE was used as membrane anchor for the antibody coupling via its free amino groups after its activation with carbodiimide. There is no necessity of antibody modification before the coupling reaction. 

An increase in therapeutic efficacy and lower toxicity was reported with liposomes where the bradykinin analogue RMP-7 was chemically attached at the end of PEG molecules of PEGylated liposomes (approximate size 70nm) [384], RMP-7 exhibits high selectivity for the B2 receptor of the BBB endothelial cells, which shrunk and let the RMP-7-PEG liposomes to pass into the brain. Actually the mechanism used in that study was based on opening the tight junctions of the BBB. Liposome-incorporated nerve growth factor (NGF) concentration increased 10 times in comparison to free NGF, while they accumulated mainly in striatum, hippocampus, and cortex. 

Recently, easy to use paclitaxel formulation LEP-ETU , demonstrated bio-equivalence with Taxol (Bristol-Myers Squibb, New York, NY) and promising activity in Phase I trials. This is mainly due to a superior paclitaxel loading capacity in the liposome bilayer, at a maximum mole percent of about 3.5%. Similarly, paclitaxel has also been encapsulated in other modern formulations of cationic lipid complexes (MBT-0206) that have been shown to be bounded and internalized selectively by angiogenic tumoral endothelial cells after intravenous administration (29). 

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