Oral empagliflozin-loaded tri-layer core-sheath fibers fabricated using tri-axial electrospinning: Enhanced in vitro and in vivo antidiabetic performance

Guler E., Nur Hazar-Yavuz A., Tatar E., Morid Haidari M., Sinemcan Ozcan G., Duruksu G., ...Daha Fazla

International Journal of Pharmaceutics, cilt.635, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 635
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.ijpharm.2023.122716
  • Dergi Adı: International Journal of Pharmaceutics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Type 2 diabetes mellitus, Empagliflozin, Core -sheath fiber, Insulin resistance, Tri-axial electrospinning, SGLT2 INHIBITOR EMPAGLIFLOZIN, PANCREATIC BETA-CELLS, DIABETES-MELLITUS, PHYSICAL-PROPERTIES, SWELLING BEHAVIOR, DRUG-RELEASE, TYPE-2, DEGRADATION, NANOTECHNOLOGY, COMPLICATIONS
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Empagliflozin (EM) was successfully loaded in polycaprolactone/poly (L-lactic acid)/polymethyl methacrylate (PCL/PLA/PMMA) fibers. In the rat β-cell line (BRIN-BD11), the insulin expression ratio of pancreatic β-cells was stimulated at high and low glucose by culturing with tri-layer EM-loaded fiber (EMF) for 48 h. The expression ratios of glucokinase and GLUT-2 proteins increased after EMF treatment. According to the in vitro drug release test, 97% of all drug contained in fibers was released in a controlled manner for 24 h. The pharmacokinetic test revealed that the bioavailability was improved ∼4.8-fold with EMF treatment compared to EM-powder and blood glucose level was effectively controlled for 24 h with EMF. Oral administration of EMF exhibited a better sustainable anti-diabetic activity even in the half-dosage than EM-powder in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, PPAR-γ, and insulin were increased while the levels of SGLT-2 and TNF-α were decreased with EMF treatment. Also, EMF recovered the histopathological changes in the liver, pancreas, and kidney in T2DM rats and protected pancreatic β-cells. Consequently, EMF is suggested as an unprecedented and promotive treatment approach for T2DM with a higher bioavailability and better antidiabetic effect compared to conventional dosage forms.