Lipid binding from aqueous solution by lipid conjugated hydroxypropyl methylcellulose (HPMC): a novel food additive for reducing cholesterol and fat intestinal absorption
Nightingale, James A. S
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This research project focuses on the development and testing of a novel, medically useful lipid or steroid sequesterant that can be administered orally. Specifically, this compound is designed to absorb cholesterol and fats from the bulk phase of the intestinal pool by sequestering these constituents and then pass out of the body with the feces. A summary of food additives as they are used to accomplish the same goal is reviewed as are the interactions of polymers with amphiphilic compounds.To accomplish the goal we have examined the physico-chemical nature of our hydrophobic affinity polymer which is created by the attachment of lipophilic moieties to a hydrophilic polymeric backbone. These compounds are specifically designed to be non-biodegradable and non-absorbable in the intestinal tract. The effectiveness of different conjugated lipids is evaluated using in vitro experiments. The lipids are octadecyl, oleyl and cholesteryl attached through glycidyl ether chemistry to hydroxyls on HPMC using stannic chloride as a catalyst.It has been found (using equilibrium dialysis experiments) that sodium taurocholate (NaTC) binds HPMC and that binding is enhanced by the attachment of glycidyl ethers to this polymer. A maximum binding of physiologically relevant NaTC concentration is reached when approximately 2-3 wt% oleyl is attached to the polymer. The binding of mixed micelles containing NaTC, sodium oleate (NaOl), lysolecithin, and cholesterol were also studied at concentrations similar to those found in the human gastrointestinal tract. It was found that all three lipids conjugated to HPMC (octadecyl, oleyl, and cholesteryl) bound NaOl and cholesterol from mixed micelles better then NaTC and this binding was enhanced as more lipid was attached to HPMC. Lipid conjugated HPMC was also shown to have in vivo activity in rats. Mechanisms governing these interactions are proposed.
- Bioengineering