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.

Synthesis, crystal structure, and thermolysis of the first tetracoordinate 1lambda4,2-selenazetidines: aziridine formation reaction from a four-membered heterocycle bearing highly coordinate selenium.

[structure: see text]. The first tetracoordinate 1lambda4,2-selenazetidines were synthesized by taking advantage of the Martin ligand and characterized by X-ray crystallographic analysis. The selenazetidines gave the corresponding aziridine and the cyclic selenenate on their thermolysis, which indicates the possibility that a highly coordinate 1,2-heterachalcogenetane may provide the corresponding heteracyclopropane regardless of the heteroatoms.

Liposomes prepared from synthetic amphiphiles. II. Their interaction with Ehrlich ascites tumor cells and tissue distribution in Ehrlich solid tumor-bearing mice.

The interaction of 99mTc-labeled liposomes prepared from synthetic amphiphiles containing amino acid residues with Ehrlich ascites tumor cells in vitro and their tissue distributions in Ehrlich solid tumor-bearing mice were investigated. The amphiphiles used were N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide N+C5Ala2C12), N,N-didodecyl-N alpha-(6-[dimethyl(2-carboxyethyl)ammonio]hexanoyl)-L- alaninamide bromide (CAC2N+C5Ala2C12) and S-[1-carboxy-2- ([2,3-bis(hexadecyloxy)propoxy]carbonyl)ethyl]homocysteine (HcyM-G2C1 6). Most of the radioactivity of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes was firmly bound to Ehrlich ascites tumor cells in vitro. On the other hand, the accumulation of three 99mTc-labeled liposomes in the tumor of Ehrlich solid tumor-bearing mice was low (about 1% dose per gram of tissue), and most of the liposomes were taken up highly in the liver and spleen of the tumor-bearing mice. However, the radioactivity of the liposomes in the tumor, especially that of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes, decreased more slowly with time than in the liver in up to 24 h after injection, suggesting that these liposomes were hard to separate from the tumor cells.