Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR.

中文翻译：

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用于提高姜黄素口服生物利用度的单宁酸涂层纳米混悬剂的开发和评价

姜黄素 (CUR) 由于具有抗炎、抗病毒、抗菌和抗肿瘤活性等多种生物学益处，已被用于治疗咳嗽、发烧、皮肤病和感染等各种疾病。然而，CUR 是 BCS 4 类组，并且由于溶解度和渗透性低而具有低生物利用度的限制。因此，本研究的目的是使用统计设计方法制备负载 CUR 的纳米混悬剂 (NSP) (CUR-NSP) 以提高 CUR 的口服生物利用度，然后开发单宁酸包衣的 CUR-NSP 以增加 CUR 的口服生物利用度。胃肠道黏膜粘连。首先，优化的 CUR-NSP 由十二烷基硫酸钠 (SDS) 和聚乙烯吡咯烷酮/醋酸乙烯酯 (PVP/VA) 组成，用单宁酸 (TA) 改性。通过激光散射分析仪测量的制剂的粒径和多分散指数分别为 127.7 ± 1.3 nm 和 0.227 ± 0.010。此外，蒸馏水 (DW) 中的沉淀为 1.52 ± 0.58%。使用差示扫描量热仪和 X 射线衍射分析，在制剂中确认了稳定的无定形 CUR，并且通过傅里叶变换红外光谱确认了 CUR-NSP 制剂涂覆有 TA。在使用浊度的粘膜粘附测定中，证实在所有 pH 条件下 TA-CUR-NSP 对粘液的亲和力高于 CUR-NSP。这意味着可以通过增加制剂在胃肠道中的保留时间来改善 CUR 的吸收。此外，药物释放曲线显示超过 80% 的释放，在细胞摄取研究中，含有作为 P-gp 抑制剂的 TA 的制剂 (TA-CUR-NSP) 的吸收增加了 1.6 倍。在抗氧化活性的评价中，TA-CUR-NSP 的 SOD 活性由于 TA 显着高，提高了细胞摄取并具有抗氧化活性。在药代动力学评估中，TA 包衣 NSP 制剂的最大药物血浆浓度比纯药物高 7.2 倍。在所有实验中，都证实 TA-CUR-NSP 是克服 CUR 口服生物利用度低的有前途的方法。在药代动力学评估中，TA 包衣 NSP 制剂的最大药物血浆浓度比纯药物高 7.2 倍。在所有实验中，都证实 TA-CUR-NSP 是克服 CUR 口服生物利用度低的有前途的方法。在药代动力学评估中，TA 包衣 NSP 制剂的最大药物血浆浓度比纯药物高 7.2 倍。在所有实验中，都证实 TA-CUR-NSP 是克服 CUR 口服生物利用度低的有前途的方法。