Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug
Authors: Said Abasse Kassim
Muhammad Sohail
Ghulam Jilany Khan
Muhammad Naveed
Muhammad Hasnat
Sana Ullah
Muhammad Tayyab Ansari
Komal Shah
Mirza Muhammad Faran Ashraf Baig
Muhammad Abbas
Journal: Journal of Food and Drug Analysis (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 3D DNA nanocube; Db–Db/mice; Nanospheres; Type 2 diabetics; Vildagliptin.
Affiliations: State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60000, Pakistan. Electronic address: ., State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China., Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, PR China; Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan., Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China., Faculty of Pharmacy, University of Central Punjab, Lahore, 54570, Pakistan., School of Pharmacy, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, PR China; Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan., Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China., Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60000, Pakistan.

Abstract:  Poor control towards glycemic levels among diabetic patients may lead to severe micro/macro-vascular and neuropathic complexities. Proper functioning of alpha-beta cells of pancreases is required to attain long term glycemic control among type 2 diabetics. The recent developments to manage diabetes are focused on controlling the insulin-glucagon secretions from the pancreases. DPP-4 inhibitors class of drugs after elevating GLP-1/GIP (incretins) levels in the blood, not only raise the insulin levels but also suppress the glucagon level. Vildagliptin (VI) is a potent DPP-4 inhibitor with least adverse events compared to other DPP-4 inhibitors. We encapsulated VI into 3D nanocube that gets bind to the DNA due to secondary amine in its chemical structure. DNA-nanocube being negatively charged was incubated with the PLL to attain positive surface. Ultimately VI loaded nanocubes were coated with the negatively charged Na-alginate via electrostatic attraction method to get stable spherical nanospheres for oral delivery of VI. Nanospheres were evaluated physically through native PAGE analysis, DSC, TGA, dissolution testing, XRD and FTIR. We attained uniformed and spherical nanospheres with stable topology, nanoscale size precision (40-150 nm in diameter), Entrapment efficiency (up to 90%), prolonged drug release (13 ± 4 h) at basic pH, and superior oral antidiabetic effects with improved GLP1 and glycemic levels. The formulated nanospheres attained size uniformity and better therapeutic outcomes in terms of reduced adverse events and better control of glycemic levels than previously reported methods with decreased dosage frequency tested in Db/Db mice. 

Retracted: No

PubPeer comments:
 Figure 2C. * Red boxes: Three bands look remarkably similar. The ones in lanes 3 and 2 appear to be surrounded by unexpected sharp transitions with respect to the background. ![file] , 
 *[above]* Fig 4A,  The prolonged release nanospheres had no damage to the endocrine portion of the pancrease after 5 months compared to the administration of the free VI solution . *[below]* Fig 5a from [Baig et al (2019)] ,  Histological studies showed no damage to any of the pancreatic cells at the end of treatment . ![file] Unexpected overlaps (after rotation, color inversion). , 
 Fig 2a,  AFM imaging of the NS3 nanosphere confirming the round and uniform shape with the size of 50-100 nm (diameter) Scale bar = 200 nm. ![file] Fig 4a from [Baig et al (2019)] ,  AFM results showed that nanoparticles with hybrid coating were smaller with uniform size distribution (30u201380 nm) that might have prolonged and superior systemic efficacy (scale bar=60 nm) . ![file] Are these the same materials? , 
 Sorry, these all belonged to a same project. Need to see if some results overlapped. Thanks for pointing out. ,