Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Center of Research Excellence for Drug Research and Pharmaceutical Industries, Pharmaceutical Technology Unit, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Int J Nanomedicine. 2022 Apr 21;17:1783-1801. doi: 10.2147/IJN.S357356. eCollection 2022.
This work was aimed to develop a Curcuma oil-based self-nanoemulsifying drug delivery system (SNEDDS) 3D-printed polypills containing glimepiride (GMD) and rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes as a model for metabolic syndrome (MS).
Compartmentalized 3D printed polypills were prepared and studied in streptozotocin/poloxamer induced diabetic/dyslipidemic rats. The pharmacokinetic parameters of GMD and RSV in the prepared polypills were evaluated. Blood glucose level, lipid profile, antioxidant, and biochemical markers activities were investigated. Also, histopathological examination of the liver and pancreas was carried out. The atherosclerotic index, the area of islets of Langerhans, and liver steatosis lesion scores were calculated.
The developed SNEDDS-loaded GMD/RSV polypills showed acceptable quality control characteristics with a high relative bioavailability of 217.16% and 224.28% for GMD and RSV, respectively, when compared with the corresponding non-SNEDDS pills. The prepared polypills showed dramatic lowering in blood glucose levels and substantial improvement in lipid profile and hepatic serum biomarkers as well as remarkable decrease in serum antioxidants in response to Poloxamer 407 intoxication. The prepared polypills decreased the risk of atherosclerosis and coronary disease by boosting the level of high-density lipoprotein and lowering both triglyceride and low-density lipoprotein. Microscopic examination showed normal hepatic sinusoids and high protection level with less detectable steatosis in the examined hepatocytes. Normal size pancreatic islets with apparently normal exocrine acini and pancreatic duct were also noticed.
This formulation strategy clearly shows the potential of the developed polypills in personalized medicine for treatment of patients with MS.
本研究旨在开发一种姜黄素油基自微乳给药系统（SNEDDS）3D 打印载有格列美脲（GMD）和瑞舒伐他汀（RSV）的复方丸，用于治疗糖尿病患者的血脂异常，作为代谢综合征（MS）的模型。
制备并研究了载有格列美脲和瑞舒伐他汀的 3D 打印复方丸在链脲佐菌素/泊洛沙姆诱导的糖尿病/血脂异常大鼠中的药代动力学参数。考察了复方丸中格列美脲和瑞舒伐他汀的药代动力学参数。检测血糖水平、血脂谱、抗氧化和生化标志物活性。还进行了肝脏和胰腺的组织病理学检查。计算了动脉粥样硬化指数、胰岛面积和肝脂肪变性病变评分。
与相应的非 SNEDDS 丸相比，开发的 SNEDDS 负载 GMD/RSV 复方丸具有可接受的质量控制特性，GMD 和 RSV 的相对生物利用度分别为 217.16%和 224.28%。与泊洛沙姆 407 中毒相比，所制备的复方丸可显著降低血糖水平，显著改善血脂谱和肝血清生物标志物，并显著降低血清抗氧化剂水平。所制备的复方丸通过提高高密度脂蛋白水平和降低甘油三酯和低密度脂蛋白来降低动脉粥样硬化和冠心病的风险。显微镜检查显示肝脏窦正常，受检肝细胞脂肪变性程度较低，保护水平较高。还观察到正常大小的胰岛，外分泌腺和胰腺导管明显正常。
这种制剂策略清楚地表明，所开发的复方丸在治疗 MS 患者的个性化医学中具有潜力。
