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使用含姜黄素的自微乳化给药系统治疗炎症性肠病:宏观与微观分析

Treatment of Inflammatory Bowel Disease by Using Curcumin-Containing Self-Microemulsifying Delivery System: Macroscopic and Microscopic Analysis.

作者信息

Ameer Nabeela, Hanif Muhammad, Abbas Ghulam, Azeem Muhammad, Mahmood Khalid, Shahwar Dure, Khames Ahmed, Eissa Essam Mohamed, Daihom Baher

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Multan 60800, Pakistan.

Department of Pharmacy, Multan University of Science and Technology, Multan 60800, Pakistan.

出版信息

Pharmaceutics. 2024 Oct 31;16(11):1406. doi: 10.3390/pharmaceutics16111406.

Abstract

The lack of local availability for drugs in the colon can be addressed by preparing a self-microemulsifying drug delivery system (SMEDDS) of curcumin (Cur) which is ultimately used for the treatment of inflammatory bowel disease (IBD). From preformulation studies, Lauroglycol FCC (oil), Tween 80 (surfactant), Transcutol HP (co-surfactant), and Avicel (solid carrier) were selected for the preparation of blank liquid and solid Cur-loaded SMEDDSs (S-Cur-SMEDDSs). Z-average size (12.36 ± 0.04 nm), zeta potential (-14.7 ± 0.08 mV), and polydispersity index (PDI) (0.155 ± 0.036) showed a comparative droplet surface area and charge of both SMEDDSs. The physicochemical stability of Cur in S-Cur-SMEDDSs was confirmed via FTIR, DSC, TGA, and XRD analyses, while morphological analysis through SEM and atomic force microscopy (AFM) confirmed Cur loading into SMEDDSs with an increased surface roughness root mean square (RMS) of 11.433 ± 0.91 nm, greater than the blank SMEDDS. Acute toxicity studies with an organ weight ratio and % hemolysis of 15.65 ± 1.32% at a high concentration of 600 mM showed that S-Cur-SMEDDSs are safe at a medium dose (0.2-0.8 g/kg/day). The excellent in vitro antioxidant (68.54 ± 1.42%) and anti-inflammatory properties (56.47 ± 1.17%) of S-Cur-SMEDDS proved its therapeutic efficacy for IBD. Finally, S-Cur-SMEDDS significantly improved acetic acid-induced IBD in albino rats through a reduction in the disease activity index (DAI) and macroscopic ulcer score (MUS) from 4.15 ± 0.21 to 1.62 ± 0.12 at 15 mg/kg/day dose, as confirmed via histopathological assay. Based on the above findings, S-Cur-SMEDDS appears to be a stable, less toxic, and more efficacious alternative for Cur delivery with strong competence in treating IBD.

摘要

通过制备姜黄素(Cur)的自微乳化药物递送系统(SMEDDS),可以解决结肠中药物局部可用性不足的问题,该系统最终用于治疗炎症性肠病(IBD)。从处方前研究中,选择月桂二醇FCC(油相)、吐温80(表面活性剂)、二乙二醇单乙醚(助表面活性剂)和微晶纤维素(固体载体)来制备空白液体和载Cur固体SMEDDS(S-Cur-SMEDDS)。Z-平均粒径(12.36±0.04nm)、zeta电位(-14.7±0.08mV)和多分散指数(PDI)(0.155±0.036)表明两种SMEDDS具有可比的液滴表面积和电荷。通过傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、热重分析(TGA)和X射线衍射(XRD)分析证实了Cur在S-Cur-SMEDDS中的物理化学稳定性,而通过扫描电子显微镜(SEM)和原子力显微镜(AFM)进行的形态分析证实Cur负载到SMEDDS中,表面粗糙度均方根(RMS)增加至11.433±0.91nm,大于空白SMEDDS。在高浓度600mM下,器官重量比和溶血率为15. The excellent in vitro antioxidant (68.54 ± 1.42%) and anti-inflammatory properties (56.47 ± 1.17%) of S-Cur-SMEDDS proved its therapeutic efficacy for IBD. Finally, S-Cur-SMEDDS significantly improved acetic acid-induced IBD in albino rats through a reduction in the disease activity index (DAI) and macroscopic ulcer score (MUS) from 4.15 ± 0.21 to 1.62 ± 0.12 at 15 mg/kg/day dose, as confirmed via histopathological assay. Based on the above findings, S-Cur-SMEDDS appears to be a stable, less toxic, and more efficacious alternative for Cur delivery with strong competence in treating IBD.65±1.32%的急性毒性研究表明,S-Cur-SMEDDS在中等剂量(0.2-0.8g/kg/天)下是安全的。S-Cur-SMEDDS优异的体外抗氧化性能(68.54±1.42%)和抗炎性能(56.47±1.17%)证明了其对IBD的治疗效果。最后,通过组织病理学分析证实S-Cur-SMEDDS在15mg/kg/天剂量下显著改善了白化病大鼠的乙酸诱导的IBD,疾病活动指数(DAI)和宏观溃疡评分(MUS)从4.15±0.21降至1.62±0.12。基于上述发现,S-Cur-SMEDDS似乎是一种稳定、低毒且更有效的Cur递送替代方案,在治疗IBD方面具有很强的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cd/11597465/66ae082b6221/pharmaceutics-16-01406-g001.jpg

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