Chitosan-coated rectangular DNA nanospheres for better outcomes of anti-diabetic drug

  • Mirza Muhammad Faran Ashraf BaigEmail author
  • Muhammad Naveed
  • Muhammad Abbas
  • Said Abasse Kassim
  • Ghulam Jilany Khan
  • Sana Ullah
  • Muhammad Sohail
  • Waqas Nawaz
  • Muhammad Rizwan Younis
  • Muhammad Tayyab Ansari
Research Paper
Part of the following topical collections:
  1. Nanoparticles in Biotechnology and Medicine


Type 2 diabetes is a metabolic disorder in which the patient fails to control the glycemic level due to compromised functioning of pancreatic α and β cells. The control of these cells is regulated by the extent of incretin peptides (GLP1 and GIP). Performance of these peptides is affected due to the increased degradation by di-peptidyl-peptidase-4 (DPP-4) enzyme in diabetic patients. Vildagliptin (VL) is one of the potential DPP-4 inhibitors and helps in controlling the glycemic level, but to deliver the VL near its site of action (intestine and blood) in a sustained manner is important. For this purpose, we used chitosan (Chit) (cationic polymer) to coat the VL-loaded DNA rectangles (negatively charged) via electrostatic attractions to make Chit-DNA-VL nanospheres. According to our results, nanospheres formulated by this novel approach were uniformed, spherical, and stable with better size control (from 40 to 400 nm in diameter). Entrapment efficiency for VL drug was up to 85%. The release of VL was extended up to 12 ± 5 h. From observed incretin and glycemic level, we concluded that the nanospheres efficiently bypassed the gastric acidity improving glycemic control in Db-Db/mouse model. Histological experiments revealed Chit-DNA-VL nanospheres did not cause damage to pancreas associated with the sustained and prolonged release of VL.


Type 2 diabetes DNA nanospheres Vildagliptin Incretins Db-Db/mouse Nanomedicine 



We highly acknowledge Prof. Xing-Hua Xia of the State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University, for the support. We are thankful to Wen Chunxia and Muhammad Hasnat for assisting us during the work. We acknowledge Maryam Sharif, Production Officer, High-Q/Pharma Pvt. Ltd., Pakistan, for donating us pure VL and polymers for this work. Special thanks to Dr. Chen Yalan of Nanjing University for the support.

Author individual contributions

MMFAB designed the study, performed most of the experiments, and prepared the manuscript. MN, MA, SAK, SU, MS, and WS assisted the work. GJK, MRY, and MTA gave expert opinions about the study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11051_2019_4534_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)


  1. Abbas M, Ahmed A, Khan GJ, Baig MMFA, Naveed M, Mikrani R, Cao T, Naeem S, Shi M, Dingding C (2019) Clinical evaluation of carcinoembryonic and carbohydrate antigens as cancer biomarkers to monitor palliative chemotherapy in advanced stage gastric cancer. Curr Probl Cancer 43:5–17CrossRefGoogle Scholar
  2. Álvarez-Lueje A, Acosta GA, Albericio F, Zapata-Urzúa C, Pérez-Ortiz M, Kogan MJ (2017) Gold nanoparticles as an efficient drug delivery system for GLP-1 peptides. Colloids Surf B: Biointerfaces 158:25–32CrossRefGoogle Scholar
  3. Baig MMFA, Khan S, Naeem MA, Khan GJ, Ansari MT (2018) Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus. Biomed Pharmacother 97:1250–1258CrossRefGoogle Scholar
  4. Baig MMFA, Naveed M, Abbas M, Chunxia W, Ullah S, Hasnat M, Shad A, Sohail M, Khan GJ, Ansari MT (2019) DNA scaffold nanoparticles coated with HPMC/EC for oral delivery. Int J Pharm 562:321–332CrossRefGoogle Scholar
  5. Ceriello A, Sportiello L, Rafaniello C, Rossi F (2014) DPP-4 inhibitors: pharmacological differences and their clinical implications. Expert Opin Drug Saf 13:57–68CrossRefGoogle Scholar
  6. Desgraz R, Kohno K, Thorel F, Chera S, Avril I, Herrera PL, Népote V (2010) Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature 464:1149–1154CrossRefGoogle Scholar
  7. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705CrossRefGoogle Scholar
  8. Elsabee MZ, Morsi RE, Al-Sabagh AM (2009) Surface active properties of chitosan and its derivatives. Colloids Surf B: Biointerfaces 74:1–16CrossRefGoogle Scholar
  9. Endo M, Yang Y, Sugiyama H (2013) DNA origami technology for biomaterials applications. Biomater Sci 1:347–360CrossRefGoogle Scholar
  10. Esposito K, Chiodini P, Maiorino MI, Capuano A, Cozzolino D, Petrizzo M, Bellastella G, Giugliano D (2015) A nomogram to estimate the hba1c response to different dpp-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients. BMJ Open 5:e005892CrossRefGoogle Scholar
  11. Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S (2007) Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia 50:1148–1155CrossRefGoogle Scholar
  12. Gan Q, Wang T (2007) Chitosan nanoparticle as protein delivery carrier—systematic examination of fabrication conditions for efficient loading and release. Colloids Surf B: Biointerfaces 59:24–34CrossRefGoogle Scholar
  13. Griffin, B., and O’Dricoll, C. (2007). Drug absorption studies. In Drug absorption studies.Google Scholar
  14. Han D, Pal S, Nangreave J, Deng Z, Liu Y, Yan H (2011) DNA origami with complex curvatures in three-dimensional space. Science 332(80):342–346CrossRefGoogle Scholar
  15. Hong F, Zhang F, Liu Y, Yan H (2017) DNA origami: scaffolds for creating higher order structures. Chem Rev 117:12584–12640CrossRefGoogle Scholar
  16. Hurst SJ, Lytton-Jean AKR, Mirkin CA (2006) Maximizing DNA loading on a range of gold nanoparticle sizes. Anal Chem 78:8313–8318CrossRefGoogle Scholar
  17. Husain T, Baig MMFA, Kakar MU, Ihsan AU, Zhou Q-G, Shumzaid M, Akabar MD, Sohail M, Naveed M, Phil L et al (2019) Chitosan oligosaccharide (COS): an overview. Int J Biol Macromol 129:827–843CrossRefGoogle Scholar
  18. Jacobsen MF, Voigt NV, Mokhir A, Besenbacher F, Tørring T, Kjems J, Mamdouh W, Subramani R, Ravnsbæk JB, Rotaru A et al (2010) Single-molecule chemical reactions on DNA origami. Nat Nanotechnol 5:200–203CrossRefGoogle Scholar
  19. Jiang Z, Shan K, Song J, Liu J, Rajendran S, Pugazhendhi A, Jacob JA, Chen B (2019) Toxic effects of magnetic nanoparticles on normal cells and organs. Life Sci 220:156–161CrossRefGoogle Scholar
  20. Khan GJ, Rizwan M, Abbas M, Naveed M, Boyang Y, Naeem MA, Khan S, Yuan S, Baig MMFA, Sun L (2018) Pharmacological effects and potential therapeutic targets of DT-13. Biomed Pharmacother 97:255–263CrossRefGoogle Scholar
  21. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B: Biointerfaces 75:1–18CrossRefGoogle Scholar
  22. Le XC, Kang D-K, Zhao W, Ali MM, Zhang Z, Ankrum JA, Zhang K, Li F (2014) Rolling circle amplification: a versatile tool for chemical biology, materials science and medicine. Chem Soc Rev 43:3324CrossRefGoogle Scholar
  23. Lin Y, Sun Z (2010) Current views on type 2 diabetes. J Endocrinol 204:1–11CrossRefGoogle Scholar
  24. Lovshin JA, Drucker DJ (2009) Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 5:262–269CrossRefGoogle Scholar
  25. Mao S, Sun W, Kissel T (2010) Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev 62:12–27CrossRefGoogle Scholar
  26. Marañón I, Marzo F, Ibáñez FC, Villarán M d C, Chávarri M, Ares R (2010) Microencapsulation of a probiotic and prebiotic in alginate-chitosan capsules improves survival in simulated gastro-intestinal conditions. Int J Food Microbiol 142:185–189CrossRefGoogle Scholar
  27. Nakayama Y, Yamaguchi H, Einaga N, Esumi M (2016) Pitfalls of DNA quantification using DNA binding fluorescent dyes and suggested solutions. PLoS One 11:e0150528CrossRefGoogle Scholar
  28. O’brien PD, Sakowski SA, Feldman EL (2014) Mouse models of diabetic neuropathy. ILAR J 54:259–272CrossRefGoogle Scholar
  29. Pugazhendhi A, Edison TNJI, Karuppusamy I, Kathirvel B (2018) Inorganic nanoparticles: a potential cancer therapy for human welfare. Int J Pharm 539:104–111CrossRefGoogle Scholar
  30. Scheen AJ (2010) Dipeptidylpeptitase-4 inhibitors (gliptins). Clin Pharmacokinet 49:573–588CrossRefGoogle Scholar
  31. Shanmuganathan R, Edison TNJI, LewisOscar F, Ponnuchamy K, Shanmugam S, Pugazhendhi A (2019) Chitosan nanopolymers: an overview of drug delivery against cancer. Int J Biol Macromol 130:727–736CrossRefGoogle Scholar
  32. Swisa A, Glaser B, Dor Y (2017) Metabolic stress and compromised identity of pancreatic beta cells. Front Genet 8:21CrossRefGoogle Scholar
  33. Taylor R (2013) Type 2 diabetes: etiology and reversibility. Diabetes Care 36:1047–1055CrossRefGoogle Scholar
  34. Todd JA (2010) Etiology of type 1 diabetes. Immunity 32:457–467CrossRefGoogle Scholar
  35. Wang W, Naveed M, Baig MMFA, Abbas M, Xiaohui Z (2018) Experimental rodent models of chronic prostatitis and evaluation criteria. Biomed Pharmacother 108:1894–1901CrossRefGoogle Scholar
  36. Yoksan R, Jirawutthiwongchai J, Arpo K (2010) Encapsulation of ascorbyl palmitate in chitosan nanoparticles by oil-in-water emulsion and ionic gelation processes. Colloids Surf B: Biointerfaces 76:292–297CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mirza Muhammad Faran Ashraf Baig
    • 1
    • 2
    Email author
  • Muhammad Naveed
    • 3
  • Muhammad Abbas
    • 4
  • Said Abasse Kassim
    • 5
  • Ghulam Jilany Khan
    • 6
    • 7
  • Sana Ullah
    • 4
  • Muhammad Sohail
    • 3
  • Waqas Nawaz
    • 8
  • Muhammad Rizwan Younis
    • 1
  • Muhammad Tayyab Ansari
    • 2
  1. 1.State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical EngineeringNanjing UniversityNanjingPeople’s Republic of China
  2. 2.Department of Pharmaceutical Chemistry, Faculty of PharmacyBahauddin Zakariya UniversityMultanPakistan
  3. 3.School of Pharmacy, Department of Clinical PharmacologyNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.School of Life Sciences, State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingPeople’s Republic of China
  5. 5.Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public HealthSoutheast UniversityNanjingPeople’s Republic of China
  6. 6.Faculty of PharmacyUniversity of Central PunjabLahorePakistan
  7. 7.Jiangsu Key Laboratory of Drug ScreeningChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  8. 8.Center for Public Health ResearchMedical School of Nanjing UniversityNanjingPeople’s Republic of China

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