Targeting of drug to the hepatocytes by fatty acids. Influence of the carrier (albumin or galactosylated albumin) on the fate of the fatty acids and their analogs.

Purpose: The aim of this study was to evaluate the potential of fatty acids as shuttles to deliver xenobiotic inside the hepatocytes as well as to study the mechanism of incorporation into isolated hepatocytes when bound to native albumin or galactosylated albumin. Theoretically, they can enter into the hepatocytes after recognition of the Fatty Acid Binding Protein (FABPPM), or remain bound to galactosylated proteins and enter into these cells by a process known as receptor mediated endocytosis after selective recognition of the asialoglycoprotein receptor (ASGPR).

Methods: We synthesized a 3H-benzoyl adduct of lauric acid (BLA) (benzoyl adduct chosen to mimic any low molecular weight drug or contrast agent), and compared the behavior of BLA with oleic acid for their binding properties to carrier-proteins and the uptake mechanism by isolated hepatocytes.

The effects of pasteurisation on albumin: an EPR binding assay for polymeric albumin.

The ability of a nitroxyl fatty acid (NFA) to bind specifically to albumin is abolished when, in the absence of stabilizers, a 4% solution of this protein is heated above a critical temperature of 60 degrees C. This treatment leads to the formation of "albumin polymers" as classically evidenced by GPC. Since the bound fraction is evidenced in EPR spectroscopy by a large anisotropic component, the presence of this anisotropy can be used in the assessment of the quality of the pharmaceutical preparations of albumin, which are usually pasteurized in order to inactivate viruses.

1,3-Diacylaminopropan-2-ols and corresponding 2-acyl derivatives as drug carriers: unexpected pharmacological properties.

The design of lipid vectors (pseudotriglycerides, PTGs), achieved by the amide isosteric substitution of the ester moieties of 1,3-diacylglycerols, is based on the structural similarity with natural triglycerides facilitating the passage of pharmacological agents across biological membranes. 2-S-Acetylthiorphan (hemiacetorphan) pseudotriglycerides, Z-glycine pseudotriglycerides and 1,3-diacylaminopropan-2-ols vector molecules differing by the nature of the acid side-chain are examined in acute toxicity, radioligand binding and guinea-pig ileum experiments. These evaluations have led us to distinguish two types of compounds.