stearates and Weight-Gain

Polyanhydrides synthesized from pure ricinoleic acid half-esters with maleic and succinic anhydrides possess desired physicochemical and mechanical properties for use as drug carriers. Ricinoleic acid maleate or succinate diacid half-esters were prepared from the reaction of crude ricinoleic acid (85% content) with succinic or maleic anhydride. The pure diacid monomers were obtained by chromatography purification through silica gel using petroleum ether/ethyl acetate/acetic acid (80/30/1 v/v/v) mixture as eluent. The pure diacid monomers (>99%) were polymerized by melt condensation to yield film-forming polymers with molecular weights exceeding 40,000 with a polydispersity of 2. Extensive biocompatibility study demonstrated their toxicological inertness and biodegradability. Their rate of elimination from rats in the course of about 4-6 weeks was faster than that found for similar fatty acid-based polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid hydrolytic degradation in 10 days. Methotrexate release from the polymers was not affected by the initial polymer molecular weight in the range of 10,000-35,000. The in vitro drug release correlated with the degradation of the polymers. The fatty acid ester monomers were further degraded to its counterparts, ricinoleic acid and succinic or maleic acid.

Topics: Animals; Biocompatible Materials; Carboxylic Acids; Decanoic Acids; Dicarboxylic Acids; Diffusion; Drug Carriers; Female; Hydrolysis; Magnetic Resonance Spectroscopy; Materials Testing; Methotrexate; Molecular Weight; Rats; Rats, Sprague-Dawley; Ricinoleic Acids; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Stearates; Succinates; Weight Gain

We examined whether a modification of a starch into an alpha-amylase resistant form can lead to a reduction of postprandial glucose and insulin responses, and consequently to a change of lipid metabolism in liver and adipose tissue. For this purpose, a processed starch was prepared using a cornstarch (70% amylose and 30% amylopectin) and monoacylglycerol (monostearate; MS), forming monostearate-starch complex (MS-treated cornstarch). When we determined in vitro hydrolysis of MS-treated cornstarch using alpha-amylase and intestinal microvillar alpha-glucosidases, the glucose production rate of the MS-treated cornstarch was slower than the non-treated cornstarch. Measurement of a transmural potential difference (delta PD) evoked by the MS-treated cornstarch in everted rat jejunum showed that the absorption rate of glucose released from the MS-treated cornstarch was also remarkably slower than that from the non-treated cornstarch. The postprandial plasma insulin response to the MS-treated cornstarch was reduced, although plasma glucose response was unchanged. In a feeding study, two groups of five or six male Wistar-strain rats were fed defined diets containing 61.1% MS-treated cornstarch or 58.2% non-treated cornstarch ad libitum for 14 days. Food intakes during the period were similar between the two groups. Feeding the MS-treated cornstarch resulted in a significantly lower maltase activity in upper jejunum than did the non-treated cornstarch feeding. The activities of lipogenic enzymes--fatty acid synthetase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G-6-PDH)--significantly decreased in epididymal adipose tissue of rats fed the MS-treated cornstarch. In the liver, FAS activity was lower in the MS-treated cornstarch group. The results indicated that MS-treated cornstarch was digested less rapidly, and lowered blood insulin response, consequently leading to a declined lipogenesis of adipose tissue and liver. This study suggests that the rate of intestinal hydrolysis of starch is an important determinant of metabolic responses such as glycemic and lipogenic responses to diets.

Topics: Adipose Tissue; Animals; Blood Glucose; Digestion; Disaccharidases; Food; Hydrolysis; Insulin; Intestine, Small; Lipids; Liver; Male; Rats; Rats, Wistar; Starch; Stearates; Weight Gain