Pairing 3D-Printing with Nanotechnology to Manage Metabolic Syndrome

Abstract

Khalid M El-Say,1,2 Raed I Felimban,3,4 Hossam H Tayeb,4,5 Adeel G Chaudhary,3,6 Abdelsattar M Omar,7– 9 Waleed Y Rizg,1,2 Fuad H Alnadwi,10 Fathy I Abd-Allah,11 Tarek A Ahmed1,2 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Center of Research Excellence for Drug Research and Pharmaceutical Industries, Pharmaceutical Technology Unit, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Center of Innovation in Personalized Medicine (CIPM), 3D Bioprinting Unit, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Center of Innovation in Personalized Medicine (CIPM), Nanomedicine Unit, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Center of Innovation in Personalized Medicine (CIPM), King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 8Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; 9Centre for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia; 10Department of Nuclear Engineering, Faculty of Engineering, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 11Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, 11651, EgyptCorrespondence: Khalid M El-Say, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia, Tel [phone], Fax [phone], Email [email protected]: 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).Methods: 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.Results: 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.Conclusion: This formulation strategy clearly shows the potential of the developed polypills in personalized medicine for treatment of patients with MS.Graphical Abstract: Keywords: 3D-printed tablets, Curcuma oil, glimepiride, metabolic syndrome, rosuvastatin, SNEDDS, nanotechnology

Keywords

• 3d-printed tablets
• curcuma oil
• glimepiride
• metabolic syndrome
• rosuvastatin
• snedds
• nanotechnology.