Drug delivery using vesicles targeted to the hepatic asialoglycoprotein receptor

Mathematical Modeling of Vesicle Drug Delivery Systems 2: Targeted Vesicle Interactions with Cells, Tumors, and the Body

“…Adding specific targeting, however, will change the pharmacokinetics of the system in the body, as the drug carriers will localize in tissues that are being targeted, and compartmental models have been altered accordingly. Dragsten et al 43 used a vesicular system that incorporated galactose-containing polymers, which target the hepatic asialoglycoprotein receptor. Due to this targeting feature, the vesicles were bound to the receptors on the cell surface and then internalized as a complex, which was also accounted for in their compartmental model.…”

“…41 To solve for these solutions, nonlinear regression programs such as WinNonlin can be used by inputting sets of experimental data. 42 Another common method involves assuming steady state-that is, setting dc/dt=0 in the ODEs-when this assumption is applicable, such as in the liver perfusion experiments performed by Dragsten and coworkers 43 that will be discussed later. In this case, equation (69) would be simplified to…”

Synthesen von Galactose‐Cluster‐haltigen Steroid‐Derivaten

“…Ausbeute den Galactose-Cluster (Gal) 3 -TRIS-Gly-SUCC-Chol (6 b) und aus 6d bzw. 6f die entsprechenden ( 2,3,4, (2,3,4,6-tetra-O-acetyl-ß-n-galactopyranosyloxyme- (2), 839 (2), 821 (7), 779 (2), 491 (1), 331 (88), 289 (12), 265 (18), 229 (14), 169 (100). …”

“…28.63,28.47 [(CH3)3C],28.43,28.09,24.66,24.27,23.01,22.77,21.44,19.52,18.96,12.07. 8) N*- succinylJ-N-ftris (2,3,4,, 25, 168.98, 139.27, 121.94, 104.23, 75.04, 73.24, 73.16, 70.69, 68.20, 67.46, 60.48, 59.50, 56.06, 55.46, 49.35, 42.47, 41.74, 37.58, 36.42, 36.00, 35.56, 35.12, 31.27, 29.68, 29.13, 27.68, 27.34, 27.23, 23.75, 23.13, 22.52, 22.25, 20.46, 18.86, 18.37, 11.51 24, 172.02, 169.14, 169.03, 138.96, 122.10, 104.04, 74.93, 73.87, 73.16, 70.69, 68.33, 67.53, 60.69, 59.33, 56.02, 55.42, 49.30, 42.88, 41.69, 40.69, 39.09, 38.81, 37.51, 36.32, 35.95, 35.53, 35.09, 31.26, 31.21, 30.51, 30.40, 27.64, 27.32, 27.16, 23.70, 23.12, 22.44, 22.17, 20.41, 18.79, 18.29, 11.43 12) succinyl J-N-Jtris- ( 2,3,4,6-tetra-O-acetyl-ß-D-galactopyranosyloxymethyl 21,171.60,170.41,170.17,169.97,169.46,168.73,139.56,122.56,101.28,74.23,70.96,70.74,70.46,68.96,68.10,66.88,61.04,59.18,56.58,55.97,49.89,44.34,42.80,42.24,39.62,37.98,36.88,36.50,36.37,…”

N-(2-Hydroxypropyl)methacrylamide copolymers targeted to the hepatocyte galactose-receptor: pharmacokinetics in DBA2 mice

“…One such approach has used drug-laden nanoparticles that rapidly associate with Kupffer cells, from where drug can diffuse into nearby tissues and produce high local concentrations (Chiannilkulchai et al, 1989). Alternatively, liver-specific targeting can be achieved intravenously using vehicles designed to interact with liver-associated receptors, such as the hepatocyte galactose receptor (Vera et al, 1985;Ceulemans et al, 1987;Dragsten et al, 1987); the fenestrated endothelial membrane of the liver allowing macromolecular access to the hepatocyte surface, combined with the abundant numbers of galactose receptors, makes them a suitable target (Fallon & Schwartz, 1989).…”