Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar Mohali, Punjab 160062, India.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar Mohali, Punjab 160062, India.
Int J Pharm. 2019 Apr 5;560:219-227. doi: 10.1016/j.ijpharm.2019.02.013. Epub 2019 Feb 15.
The present investigation highlights the development of D-α-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™ 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 ∼14-fold higher Caco-2 cell uptake and ∼12.8-fold increased ex vivo intestinal permeability. Also, the AUC of CUR nanocapsules in Sprague Dawley rats was increased by ∼12 folds and MRT ∼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.
本研究强调了 D-α-生育酚聚乙二醇 1000 琥珀酸酯（Tocophersolan；TPGS）稳定的脂质纳米囊的开发，以提高姜黄素（CUR）的口服生物利用度和通透性。对不同的脂质、不同浓度的 TPGS 和不同的药物：脂质比进行了脂质纳米囊的优化，并进一步进行了冷冻干燥。随后，对其进行了粉末 X 射线衍射、透射电子显微镜分析，并对体外释放研究、Caco-2 细胞摄取研究、离体肠通透性和体内药代动力学性能进行了评价。优化的脂质纳米囊表现出理想的质量特性（平均粒径为 190nm、多分散指数为 0.240 和平均包封效率为 51.06±7.27），采用 Maisine™ 35-1 作为脂质载体、0.05%TPGS 和 CUR：脂质比为 5：10，并表现出持续释放的双相模式。它们在模拟胃肠道液体和储存稳定性方面表现出优异的稳定性。CUR 纳米囊在 Caco-2 细胞中的摄取量增加了约 14 倍，离体肠通透性增加了约 12.8 倍。此外，与 CUR 水溶液相比，CUR 纳米囊在 Sprague Dawley 大鼠中的 AUC 增加了约 12 倍，MRT 增加了约 2.47 倍。因此，脂质纳米囊对提高 CUR 的通透性和口服生物利用度具有积极影响。
