Tripathi Shailja, Kushwah Varun, Thanki Kaushik, Jain Sanyog
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Nanomedicine. 2016 Aug;12(6):1431-43. doi: 10.1016/j.nano.2016.03.003. Epub 2016 Mar 29.
The present study aimed to develop quercetin, resveratrol and genistein loaded self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to improve their oral bioavailability and antioxidant potential. The size and PDI of the optimized formulation were found to be <200nm and <0.3, respectively. DPPH scavenging assay showed comparable antioxidant activity of antioxidant loaded SNEDDS to free antioxidants combination. Furthermore, coumarin-6 loaded SNEDDS formulation showed rapid internalization within 1h of incubation by Caco-2 cells. Moreover, the pharmacokinetic studies in rats for the optimized formulation and free antioxidant suspension were performed. SNEDDS have significantly increased the Cmax and area under curve (AUC) of all three antioxidants. The SNEDDS demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5 fold in case of resveratrol and ~2.8 fold in case of genistein as compared to free antioxidants suspension. Finally, the prophylactic antitumor efficacy of developed formulation was tested against DMBA induced breast cancer model in rats, which demonstrated enhanced abeyance towards the tumor growth as compared to free antioxidants.
本研究旨在通过质量源于设计（QbD）方法开发载有槲皮素、白藜芦醇和染料木黄酮的自纳米乳化药物递送系统（SNEDDS），以提高它们的口服生物利用度和抗氧化潜力。优化后的制剂的粒径和多分散指数（PDI）分别被发现小于200nm和小于0.3。二苯基苦味酰基自由基（DPPH）清除试验表明，载有抗氧化剂的SNEDDS与游离抗氧化剂组合具有相当的抗氧化活性。此外，载有香豆素-6的SNEDDS制剂在与Caco-2细胞孵育1小时内显示出快速内化。此外，还对大鼠进行了优化制剂和游离抗氧化剂悬浮液的药代动力学研究。SNEDDS显著提高了所有三种抗氧化剂的最大血药浓度（Cmax）和曲线下面积（AUC）。与游离抗氧化剂悬浮液相比，SNEDDS显示槲皮素的口服生物利用度提高了约4.27倍，白藜芦醇提高了约1.5倍，染料木黄酮提高了约2.8倍。最后，对所开发制剂在大鼠二甲基苯并蒽（DMBA）诱导的乳腺癌模型中的预防性抗肿瘤疗效进行了测试，结果表明与游离抗氧化剂相比，其对肿瘤生长的抑制作用增强。
