Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus
Authors: Ghulam Jilany Khan
Muhammad Ahsan Naeem
Sara Khan
Mirza Muhammad Faran Ashraf Baig
Muhammad Tayyab Ansari
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA nanospheres; DPP-4; Db/Db mouse; Diabetes mellitus type 2; Eudragit
Affiliations: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan; School of Chemistry and Chemical Engineering, Nanjing University, PR China., Department of Pharmaceutical Chemistry, University College of Pharmacy, University of the Punjab, Lahore Pakistan., Department of Mechatronics and Control Engineering, University of Engineering and Technology, Lahore, Pakistan., Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China; Department of Pharmacology, Faculty of Pharmacy (FOP), University of Central Punjab, Lahore, Pakistan; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. Electronic address: ., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

Abstract:  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. 

Retracted: No

PubPeer comments:
 **Figure 4:** Multiple stretches compressions from the same ROI and reassemble as a figure ![file] , 
 Agarose gel from Figure 3 and one item from Figure 4 appears on a different paper from the same 1st author: https: doi.org 10.1016 j.jddst.2019.05.023 (Figure 4) ![file] , 
 *[left]* Fig 5A,  FTIR of (a) formulation V3, (b) V6, (c) Eud-DNA nanospheres without VG (d) Pure VG. All the formulations containing VG showed characteristic VG peak at 1654 nm proved that VG is chemically unchanged . *[middle]* Fig 5A from  Evaluation of chitosan eudragit hybrid coating over cubic DNA nanospheres with superior stability and therapeutic outcomes ([Baig et al 2019b] ),  FTIR analysis depicted chemical and physical stability visualizing all important peaks with slight shifts due to physical entrapments . The direction of the horizontal axis is not consistent across panels. *[right]* Fig 3b from  Chitosan-coated rectangular DNA nanospheres for better outcomes of anti-diabetic drug ([Baig et al 2019c] ),  FTIR analysis of the NPs showing chemical stability of the DNA and the VL with the chitosan showing all the individual peaks clearly. ![file] The descriptions of the NPs is not entirely consistent. Using triangular vs. cubic DNA constructs as cores for the NPs seems to make no difference at all. , 
 Sorry, these all belonged to a same project. Need to see if results overlapped. Thanks for pointing out. , 
 Fig 6A.  After the end of treatment course, H E staining of pancreatic tissue showed no sign of Pancreatitis Pancreatic cancer in both control group as well as EudDNA-VG administered group. Overlap marked. ![file] , 
 #1 Note also that the background is wallpaper. ![file] ,