Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Molecules. 2021 Mar 6;26(5):1435. doi: 10.3390/molecules26051435.
Despite its proven efficacy in diverse metabolic disorders, quercetin (QU) for clinical use is still limited because of its low bioavailability. D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) is approved as a safe pharmaceutical adjuvant with marked antioxidant and anti-inflammatory activities. In the current study, several QU-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were investigated to improve QU bioavailability. A reversed phase high performance liquid chromatography (RP-HPLC) method was developed, for the first time, as a simple and sensitive technique for pharmacokinetic studies of QU in the presence of TPGS SNEDDS formula in rat plasma. The analyses were performed on a Xterra C column (4.6 × 100 mm, 5 µm) and UV detection at 280 nm. The analytes were separated by a gradient system of methanol and phosphate buffer of pH 3. The developed RP-HPLC method showed low limit of detection (LODs) of 7.65 and 22.09 ng/mL and LOQs of 23.19 and 66.96 ng/mL for QU and TPGS, respectively, which allowed their determination in real rat plasma samples. The method was linear over a wide range, (30-10,000) and (100-10,000) ng/mL for QU and TPGS, respectively. The selected SNEDDS formula, containing 50% / TPGS, 30% polyethylene glycol 200 (PEG 200), and 20% / pumpkin seed oil (PSO), showed a globule size of 320 nm and -28.6 mV zeta potential. Results of the pharmacokinetic studies showed 149.8% improvement in bioavailability of QU in SNEDDS relative to its suspension. The developed HPLC method proved to be simple and sensitive for QU and TPGS simultaneous determination in rat plasma after oral administration of the new SNEDDS formula.
尽管槲皮素（QU）在多种代谢紊乱中已被证实具有疗效，但由于其生物利用度低，临床应用仍受到限制。D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）已被批准为一种安全的药物辅料，具有显著的抗氧化和抗炎活性。在本研究中，研究了几种载有 QU 的自微乳给药系统（SNEDDS），以提高 QU 的生物利用度。首次建立了反相高效液相色谱（RP-HPLC）法，用于在含有 TPGS SNEDDS 配方的情况下，在大鼠血浆中进行 QU 的药代动力学研究。分析在 Xterra C 柱（4.6×100mm，5μm）上进行，并在 280nm 处进行紫外检测。通过甲醇和 pH3 的磷酸盐缓冲液的梯度系统分离分析物。所建立的 RP-HPLC 方法显示 QU 和 TPGS 的检测限（LODs）分别为 7.65 和 22.09ng/mL，定量限（LOQs）分别为 23.19 和 66.96ng/mL，允许在真实的大鼠血浆样品中进行测定。该方法在较宽的范围内具有线性关系，QU 和 TPGS 的线性范围分别为（30-10000）和（100-10000）ng/mL。所选的 SNEDDS 配方含有 50%/TPGS、30%聚乙二醇 200（PEG 200）和 20%/南瓜籽油（PSO），粒径为 320nm，zeta 电位为-28.6mV。药代动力学研究结果表明，与 QU 混悬剂相比，SNEDDS 中 QU 的生物利用度提高了 149.8%。该方法简单、灵敏，可用于大鼠口服新 SNEDDS 配方后同时测定 QU 和 TPGS。
