Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus.
Diabetes mellitus type 2 is a multidimensional disease associated with poor glycemic control through compromised sensitivity of pancreatic islet α and β cells against glucose and dwindled secretion of insulin which is linked with the quantity of incretin hormones that are abridged by dipeptidyl peptidase-4 (DPP-4) in diseased condition. Vildagliptin (VG) inhibits DPP-4 therefore regulates the incretins that conversely maintains glycemic control. The safe reach and absorption of VG from intestine was dubious. Therefore we used Electrostatic Attraction Method to develop drug loaded DNA nanotechnology triangles coated by Eudragit (Eud) to make stable nanospheres of Vildagliptin (VG). We further analyzed the formulated nanospheres by AFM, XRD, DSC, SEM, TGA, ATR-FTIR and native PAGE. Additionally the efficacy of formulated nanospheres for drug release and glycemic control was assessed in Db/Db mouse. Our results showed that formulated nanospheres are smooth, spherical, stable and uniform in size ranging from 500 to 2000 nm with drug entrapment efficiency up to 95 ± 2% and extended drug release up to 15 ± 2 h. FTIR and DSC results confirmed the absence of VG-DNA-Eud interaction and XRD studies revealed a change in the crystalline status of the VG in nanospheres. Ex-vivo studies indicate that Eud-DNA-VG nanospheres effectively bypasses the acidic pH of the stomach and enhances glycemic control in Db/Db mouse without any risk of pancreatitis or pancreatic cancer. To the best of our knowledge, this is the first study conclusively reporting that VG loaded DNA Nano-architects coated with Eudragit are stable, safe and may improve therapeutic outcomes after oral delivery.
['Baig|Mirza Muhammad Faran Ashraf|MMFA|', 'Khan|Sara|S|', 'Naeem|Muhammad Ahsan|MA|', 'Khan|Ghulam Jilany|GJ|', 'Ansari|Muhammad Tayyab|MT|']
D000218:Adamantane D000284:Administration, Oral D000818:Animals D001786:Blood Glucose D003460:Crystallization D004247:DNA D003692:Delayed-Action Preparations D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D054873:Dipeptidyl-Peptidase IV Inhibitors D004337:Drug Carriers D016503:Drug Delivery Systems D065546:Drug Liberation D007004:Hypoglycemic Agents D008297:Male D051379:Mice D054118:Nanospheres D036103:Nanotechnology D009570:Nitriles D010316:Particle Size D011109:Polymethacrylic Acids D011759:Pyrrolidines D000077597:Vildagliptin
Vildagliptin DNA nanospheres Eudragit Diabetes mellitus type 2 DPP-4 Db/Db mouse Eudragit-RL100 (PubChem CID: 104804) Eudragit-RS100: (PubChem CID: 104931) GIP GLP-1 Vildagliptin (PubChem CID: 6918537)