Engineered chylomicron mimicking carrier emulsome for lymph targeted oral delivery of methotrexate

The aim of the present study was to develop chylomicron mimicking carrier emulsome for oral lymphatic delivery of methotrexate (MTX), an anticancer drug. The compritol 888 ATO (CA) was used as lipid core and soya lecithin (PC) as stabilizer. The optimized emulsome (1:1.2 mole ratio of CA:PC) showed mean particle size of 160.3 +/- 10.2 nm and with 72.8 +/- 6.5% drug entrapment efficiency. The differential scanning calorimetric studies revealed a depression in endothermic onset for MTX loaded emulsome. The rapid burst release of the drug was observed in simulated gastric fluid (SGF pH 1.2) with significant increase in particle size of emulsome. However in simulated intestinal fluid (SIF, pH 7.4) a slow and consistent release of the drug was obtained over period of 24 h. Storage stability studies were performed at different temperatures (4 +/- 1 and 25 +/- 1 degrees C) for 3 months which suggested that EML remain more stable when stored at refrigerated condition. The in vivo studies were carried out on albino rats and response was estimated collecting blood and lymph both. The pharmacokinetic parameters C-max, t(max) and AUC(0 -> 12 h) after duodenal administration of optimized emulsomal formulation and plain MTX solution were 7.1 and 2.4 mu g/mL, 4 and 1 h, 40.45 and 7.2 h mu g/mL respectively. The relative bioavailability of MTX was enhanced nearly 5.7 times with optimized EML formulation when compared to plain MTX solution with higher uptake and longer residence time of MTX molecules in lymphatics. Thus, emulsome could be used as lymphotropic carrier for delivery of bioactive(s) and hence for bioavailability enhancement. (C) 2009 Elsevier B.V. All rights reserved.