Use of the intestinal bile acid transporter for the uptake of cholic acid conjugates with HIV-1 protease inhibitory activity.

Purpose: To investigate the ability of the human intestinal bile acid transporter to transport cholic acid conjugates with potential HIV-1 protease inhibitory activity.

Methods: Cholic acid was conjugated at the 24 position of the sterol nucleus with various amino acids and amino acid analogs. The CaCo-2 cell line was used as a model to investigate the interaction of these bile acid conjugates with the human intestinal bile acid transporter.

In vitro gene delivery by degraded polyamidoamine dendrimers.

Transfection of cultured cells has been reported using complexes between DNA and spherical cationic polyamidoamine polymers (Starburst dendrimers) that consist of primary amines on the surface and tertiary amines in the interior. The transfection activity of the dendrimers is dramatically enhanced (> 50-fold) by heat treatment in a variety of solvolytic solvents, e.g.

Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes.

Efforts to overcome rapid uptake of liposomes by cells of the mononuclear phagocytic system (MPS) have identified that lipids derivatized with the hydrophilic polymer poly(ethylene glycol) (PEG) have many advantages. The structure-function relationship of PEG-derivatized phosphatidylethanolamine (PEG-PE) has been examined by studies of blood lifetime and tissue distribution in both mice and rats. Liposomes composed of phosphatidylcholine (PC), cholesterol, and 7.

Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.

The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules.

Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo.

Novel synthetic lipid derivatives of poly(ethylene glycol) (PEG) have been synthesized and tested for their ability to decrease uptake of liposomes into the mononuclear phagocyte system (MPS, reticuloendothelial system) in mice and to prolong circulation half-lives of liposomes. A carbamate derivative of PEG-1900 with distearoylphosphatidylethanolamine (PEG-DSPE) had the greatest ability to decrease MPS uptake of liposomes, at optimum concentrations of 5-7 mol% in liposomes composed of sphingomyelin/egg phosphatidylcholine/cholesterol (SM/PC/Chol, 1:1:1, molar ratio). Results obtained with this compound were equivalent to results previously obtained with 10 mol% monosialoganglioside GM1 in liposomes of similar compositions (Allen, T.

Synthesis of carboxyacyl derivatives of phosphatidylethanolamine and use as an efficient method for conjugation of protein to liposomes.

Carboxyacyl derivatives of phosphatidylethanolamine with different chain length were synthesized. These compounds were generally prepared by conversion of an appropriate dicarboxylic acid to its anhydride with dicyclohexylcarbodiimide, then reaction with phosphatidylethanolamine (PE) and triethylamine, followed by acidification. These derivatives, when incorporated into liposomes, were highly efficient in conjugating protein to liposomes.

Use of a reversed-phase evaporation vesicle formulation for a homogeneous liposome immunoassay.

Complement-mediated release of enzyme molecules from reversed-phase evaporation vesicles serves as the basis of the sensitive homogeneous immunoassay reported here. We found it necessary to co-entrap the substrate glucose 6-phosphate with the bacterial enzyme glucose-6-phosphate dehydrogenase (EC 1.1.

A Picolinic Acid Derivative: A Plant Growth Regulator.

4-Amino-3,5,6-trichloropicolinic acid is more toxic to many broad-leaved plants than 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. It is comparable in absorption by foliage, in translocation, and in soil-leaching characteristics; in soil, however, it retains its activity for a longer time.