Relationship between the Anchor Structure of the Galactosyl Ligand for Liposome Modification and Accumulation in the Liver

• Published in: Biological & pharmaceutical bulletin Vol. 18; no. 1; pp. 82 - 88
• Main Authors: MURAHASHI, Naokazu, SASAKI, Atsushi, HIGASHI, Kunio, MORIKAWA, Anri, YAMADA, Harutami
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1995; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Biological and medical sciences; Carbohydrate Sequence; Chromatography, Gel; Chromatography, High Pressure Liquid; galactose; Galactose - chemistry; Galactose - pharmacokinetics; General pharmacology; Glucuronates - chemistry; Glucuronates - metabolism; Inulin - administration & dosage; Inulin - chemistry; Ligands; liposome; Liposomes - chemistry; Liposomes - pharmacokinetics; liver; Liver - metabolism; Male; Medical sciences; Molecular Sequence Data; Palmitic Acids - chemistry; Palmitic Acids - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Sialic Acids - chemistry; Sialic Acids - metabolism; Spectrophotometry, Ultraviolet; targeting; Tissue Distribution; Rat; Liver; Structure metabolism relation; Rodentia; Liposome; Drug carrier; Vertebrata; Mammalia; Animal; Distribution; Structure modification; Galactose; Pharmacokinetics
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.82

Liposomes which have been modified with (8-hexadecanoylamido-3, 6-dioxaoctyl)-β-D-galactose (Gal-t-pa), a straight chain palmitoyl derivative, and are composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH), and dicetyl phosphate (DCP) at a ratio of 10 : 10 : 1, showed the same accumulation in the liver as the control liposome. Also, liposomes which have been modified with {8-(2-hexadecyloctadecanoylamido)-3, 6-dioxaoctyl}-β-D-galactoside (Gal-t-psa) showed remarkable accumulation in the liver. The accumulation of liposomes modified with galactose derivatives in the rat liver differed markedly according to the anchor structure. To clarify the cause of this finding, we produced [3H] inulin entrapped [14C] Gal-t-pa modified double label liposomes and evaluated changes in their rat plasma concentration, distribution in the organs, and the in vitro interaction with rat plasma. [14C] Gal-t-pa on the liposome surface bound to serum albumin and was released, resulting in no accumulation in the liver. In addition, sialic acid palmitoyl derivatives and glucuronic acid palmitoyl derivatives behaved similarly. As with the galactose derivatives, they also bound to serum albumin, being released from liposomes. These results suggest that adequate attention should be paid to the anchor structure of the ligand, in order to incorporate a recognition element into liposomes for transport to cells.