Effects of alkyl glycosides incorporated into liposomes prepared from synthetic amphiphiles on their tissue distribution in Ehrlich solid tumor-bearing mice.
A study of the effects of alkyl glycosides incorporated into synthetic liposomes with respect to their stability, their in vivo distribution in Ehrlich solid tumor-bearing mice and their in vitro interaction with liver cells was undertaken. The synthetic liposomes were prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) and labeled with 99mTc. n-Dodecyl glucoside (DG) and n-dodecyl sucrose (DS) were used as alkyl glycosides. The stability was hardly changed by incorporation of alkyl glycosides into the liposomes in saline and serum. The uptake of DG- and DS-modified N+C5Ala2C12 liposomes decreased in liver and spleen compared with that of unmodified N+C5Ala2C12 liposomes, resulting in an increase in blood and other tissues such as tumor, duodenum and kidney, where the DS-modified N+C5Ala2C12 liposomes had a marked tendency. It was observed with electron micrographs that the size of N+C5Ala2C12 liposomes became small by incorporation of alkyl glycoside. The smaller N+C5Ala2C12 liposomes were found to result in the lower uptake in liver. The interaction of the liposomes with liver cells in vitro indicated that both DG- and DS-modified liposomes had a low affinity for liver cells compared with the unmodified liposomes and the extent of interaction of the DS-modified liposomes was weaker than that of the DG-modified liposomes.
Daicho
Y
Y
Laboratory of Radiation Chemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Japan.
Okada
S
S
Goto
R
R
D000478:Alkylation; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002478:Cells, Cultured; D004337:Drug Carriers; D005960:Glucosides / Q000378:metabolism; D006027:Glycosides / Q000493:pharmacokinetics*; D007700:Kinetics; D008081:Liposomes / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D012965:Sodium Chloride; D013395:Sucrose / Q000378:metabolism; D014018:Tissue Distribution
D004337:Drug Carriers; D005960:Glucosides; D006027:Glycosides; D008081:Liposomes; D012965:Sodium Chloride; D013395:Sucrose; C038732:dodecyl glucoside