Arabinogalactan for hepatic drug delivery.
Arabinogalactan, a polysaccharide from the tree Larix occidentalis, has been purified and its biological and physical properties described. Intravenous injection of radiolabeled arabinogalactan (4 mg/kg) in rats resulted in 52.5% of the dose being present in the liver, while prior injection of asialofetuin (100 mg/kg) reduced hepatic radioactivity to 3.54%. Gel chromatography indicates arabinogalactan is a single species of 19 kDa, while light scattering gave a molecular weight of 40 kDa. Glycosyl linkage analysis of arabinogalactan is consistent with a highly branched structure comprising a backbone of 1,3-linked galactopyranose connected by 1,3-glycosidic linkages, comprised of 3,4,6-,3,6-, and 3,4- as well as 3-linked residues. In the carbon-13 NMR spectra, the major resonances of arabinogalactan are assigned to beta-galactopyranose, beta-arabinofuranose, and beta-arabinopyranose. Arabinogalactan produced no adverse reactions in single intravenous dose (mouse, 5000 mg/kg) and repeat dose toxicity studies (rats, 500 mg/kg/day, 90 days). When tritiated arabinogalactan was injected, radioactivity cleared from the liver with a half-life of 3.42 days. Arabinogalactan has properties that make it suitable as a carrier for delivering diagnostic or therapeutic agents to hepatocytes via the asialoglycoprotein receptor.
Groman
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EV
Advanced Magnetics, Inc., Cambridge, Massachusetts 02138.
Enriquez
P M
PM
Jung
C
C
Josephson
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D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000494:pharmacology; D002236:Carbohydrate Conformation; D003037:Cobalt Radioisotopes; D004337:Drug Carriers; D004355:Drug Stability; D060748:Fetuins; D005685:Galactans / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000494:pharmacology
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D003037:Cobalt Radioisotopes; D004337:Drug Carriers; D060748:Fetuins; D005685:Galactans; D011956:Receptors, Cell Surface; D000509:alpha-Fetoproteins; C017029:asialofetuin; C005653:arabinogalactan