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Lymphatic Transport (lymphatic + transport)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Comparison of the lymphatic transport of a lipophilic drug from vehicles containing ,-tocopherol and/or triglycerides in rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2001
P. B. Nielsen
The applicability of ,-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28,179, in rats after administration to the stomach in an ,-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an ,-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of ,-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an ,-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of ,-tocopherol was less than 1 mg 24 h after administration of both emulsions containing ,-tocopherol. The absorption of Lu28,179 from the ,-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an ,-tocopherol/sesame oil emulsion, the recovery of Lu28,179 increased sevenfold to 0.35%. However, after administration of Lu28,179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that ,-tocopherol did not promote lymphatic absorption of Lu28,179 and thus was not a good lymphotropic carrier, as compared with sesame oil. ,-Tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed ,-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28,179. [source]

Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion in Abcg8,/, mice,,

HEPATOLOGY, Issue 4 2007
Helen H. Wang
Sitosterolemia is caused by mutations in either ABCG5 or ABCG8, but simultaneous mutations of these genes have never been observed. To explore whether ABCG8, the sterol efflux (hemi-)transporter, plays a major role in determining intestinal absorption efficiency and hepatic secretion rates of cholesterol and sitostanol, we performed direct measurements of the absorption and lymphatic transport of these sterols in mice with chronic biliary and lymphatic fistulae, as well as the transport rates of radiolabeled cholesterol and sitostanol from plasma high-density lipoprotein (HDL) into bile in male Abcg8,/, and wild-type mice. We observed that the absorption and lymphatic transport rates of radiolabeled cholesterol and sitostanol were increased by ,40% and ,500%, respectively, in Abcg8,/, mice in the setting of constant intraduodenal infusion of micellar taurocholate and lecithin. Both strains displayed identical intestinal Npc1l1 expression levels and small intestinal transit rates. After 45 minutes of intraduodenal infusion, acute intestinal uptake rates of trace [14C]cholesterol and [3H]sitostanol were essentially similar in both groups of mice with intact biliary secretion. Furthermore, in wild-type mice, mass transport rate of [3H]sitostanol from plasma HDL into bile was significantly faster than that of [14C]cholesterol; however, no [3H]sitostanol and only traces of [14C]cholesterol were detected in bile of Abcg8,/, mice. Conclusion: Deletion of the Abcg8 gene alone significantly increases the mass of intestinal cholesterol and sitostanol absorption and reduces but does not eliminate hepatic secretion of cholesterol. Moreover, the mutation has no influence on acute uptake of cholesterol and sitostanol by the enterocyte nor small intestinal transit time. (HEPATOLOGY 2007;45:998,1006.) [source]

Evidence for lymphatic transport of insulin by topically applied biphasic vesicles

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2003
Martin J. King
ABSTRACT The cutaneous delivery pathway through the lymphatics of a novel transdermal lipid-based delivery system (biphasic vesicles), which was previously shown to deliver sustained physiological levels of basal insulin in a pain-free manner across the skin, was evaluated in a diabetic rat model. Transdermal patches (one per rat) containing insulin in biphasic vesicles (1,10 mg recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 73 h. Blood glucose was monitored approximately every 2,10 h using a Lifescan glucose meter. Inguinal lymph node insulin levels were analysed by ELISA. Insulin in the lymph nodes increased in a dose- and time-dependent manner. Maximal transdermal insulin concentrations in the lymph nodes were observed with both 140 IU (5 mg: 43.0 + 18.0 ,IU mg,1 (mean + s.e.m., n = 4)) and 280 IU (10 mg: 48.0 + 19.6 ,IU mg,1 (mean + s.e.m., n = 4)) doses of recombinant insulin at t = 73 h. The level of insulin in the lymph nodes after subcutaneous injection of 1 mg insulin at the peak blood glucose response was 35.8 ,IU mg,1 (n = 2), before falling to 0.35 ,IU mg,1 by t = 48 h (n = 2). The lymphatics is involved in the transdermal insulin delivery by biphasic vesicles. This is the first report on the lymphatic transport of a protein after non-invasive topical application on the skin. [source]

Comparison of the lymphatic transport of a lipophilic drug from vehicles containing ,-tocopherol and/or triglycerides in rats

Does stereoselective lymphatic absorption contribute to the enantioselective pharmacokinetics of halofantrine In Vivo?

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2003
David M. Shackleford
Abstract Halofantrine (Hf) is a chiral, lipophilic phenanthrene methanol antimalarial which exhibits both enantioselective plasma pharmacokinetics and extensive lymphatic absorption when administered postprandially. In order to determine whether enantioselective lymphatic absorption contributes to the previously reported enantioselective pharmacokinetics of Hf, lymph samples collected from thoracic duct-cannulated dogs dosed with racemic Hf (100 mg, administered postprandially) were assayed with a chiral HPLC method capable of quantifying the relative amounts of (+)- and (,)-Hf. During the period when the majority (>95%) of Hf transport into lymph occurred (0,5 h post dose), essentially equal amounts of the two enantiomers were present in the intestinal lymph. At later times (e.g. 5,12 h post dose), there was a steady increase in the fraction of (+)-Hf present in lymph. The trends evident at later time points most likely reflect an increase in the proportion of (+)-Hf present in systemic blood, (resulting from enantioselective systemic metabolism) and a corresponding increase in (+)-Hf in the thoracic lymph by equilibration of drug across blood and lymphatic capillaries, as opposed to enantioselective lymphatic transport per se. This study was the first to examine the possibility of stereoselectivity in lymphatic transport, however, the data suggest that drug absorption (at least in the case of halofantrine) via the intestinal lymphatics is not enantioselective. Copyright © 2003 John Wiley & Sons, Ltd. [source]