Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 560, Issue -, Pages 219-227Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2019.02.013
Keywords
Curcumin; Nanocapsules; Permeability; Oral bioavailability
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The present investigation highlights the development of D-alpha-Tocopheryl polyethylene glycol 1000 succinate (Tocophersolan; TPGS) stabilized lipid nanocapsules for enhancing the oral bioavailability and permeability of curcumin (CUR). Lipid nanocapsules were optimized for different lipids, different concentrations of TPGS and different drug: lipid ratio and were further lyophilized. Subsequently, they were characterized by powder X-ray diffraction, Transmission electron microscopy and also evaluated for in vitro release study, Caco-2 cell uptake study, ex vivo intestinal permeability and in vivo pharmacokinetic performance. Optimized lipid nanocapsules exhibited desirable quality attributes (average particle size of 190 nm, polydispersity index of 0.240 and average % entrapment efficiency of 51.06 +/- 7.27) employing Maisine (TM) 35-1 as a lipid carrier, 0.05% TPGS and CUR: lipid ratio of 5:10 and showed sustained release biphasic pattern. They showcased excellent stability in simulated gastrointestinal fluids and storage stability. The CUR nanocapsules exhibited similar to 14-fold higher Caco-2 cell uptake and similar to 12.8-fold increased ex vivo intestinal permeability. Also, the AUC of CUR nanocapsules in Sprague Dawley rats was increased by similar to 12 folds and MRT similar to 2.47-folds as compared to aqueous CUR suspension. Thus, lipid nanocapsules possessed a positive impact on improving the permeability and oral bioavailability of CUR.
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