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PLL-alginate and the HPMC-EC hybrid coating over the 3D DNA nanocubes as compact nanoparticles for oral administration

  • Mirza Muhammad Faran Ashraf BaigEmail author
  • Muhammad Sohail
  • Ali Asghar Mirjat
  • Muhammad Naveed
  • Fatima Majeed
  • Faisal Raza
  • Muhammad Asim Farooq
  • Reyaj Mikrani
  • Salman Khan
  • Muhammad Abbas
  • Sana Ullah
  • Muhammad Hasnat
  • Wen Chunxia
  • Ghulam Jilany Khan
  • Muhammad Tayyab Ansari
Original Article

Abstract

Diabetes Type 2 has been quite difficult to treat/manage with elevated fasting/postprandial glycemic levels. Although this metabolic disorder mostly affected older people, recently a big population of young people developed either pre-diabetes or maturity-onset diabetes-mellitus of young (MODY). A Sulphonylurea class of drugs (SUs) has been used for decades to treat/manage diabetes Type 2. However, sustained release formulations of SUs pose a great risk of hypoglycemia due to the burst insulin release with poor control on fasting glycemic levels with pancreatic beta-cells to undergo exhaustion and decreased beta-cells mass with time and decreased the ability to produce/release insulin on chronic stages. This complication augments alpha cells to secrete glucagon due to feedback stimulation. However, Vildagliptin (VI) as a potent DPP-4 inhibitor has incretin-mediated (GLP1 and GIP), and glucose-dependent mechanism of action to stimulate beta-cells postprandial and wreck the secretion of glucagon from alpha cells. It was reported to improve beta-cells mass with time due to hormonal (incretin elevating) mechanism of action and need to decrease the dose after a few years of administration due to improved ability of the pancreas to release insulin. Herein, we report gastro-retentive HPMC-EC/Alg-PLL hybrid coating over the VI loaded 3D DNA-nanocubes through the electrostatic-interactions/solvent-evaporation techniques to make HPMC-EC/Alg-PLL-DNA-VI hybrid nanoparticles. We attained more stable nanoparticles with better size-uniformity (25–50 nm diameter), having a smooth surface with Entrapment efficiency (E.E%) ≈ 95% and sustained VI release up to 18 ± 4 h than our previous studies (35–2500 nm diameter) (E.E% ≈ 74–92% and prolonged VI release ≈ 15 ± 6 h). We observed superior in vivo GLP-1 and glycemic levels. Hence, hybrid nanoparticles being gastro-retentive released VI slowly to the target site (intestine + blood) in vivo without damaging the islets of Langerhans observed from the histological analysis of the pancreas after treatment duration.

Keywords

Diabetes type 2 HPMC-EC/Alg-PLL-DNA-Vl hybrid nanoparticles, GLP1 

Notes

Acknowledgements

We highly acknowledge State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University for support. We acknowledge Maryam Sharif, Production Officer, High-Q/Pharma Pvt. Ltd. Pakistan for donating us pure-VI and polymers for this work. Special thanks to Dr. Chen Yalan of Nanjing University for support.

Author contributions

MMFAB designed the study, and performed most of the experiments and prepared the manuscript. MS, AAM, MN, FM, FR, MAF, RM, SK, MA, SU and MH assisted the work. WC, GJK and MTA gave expert opinions about the study.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

13204_2019_1075_MOESM1_ESM.docx (36 kb)
Supplementary material 1 (DOCX 35 kb)

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Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  • Mirza Muhammad Faran Ashraf Baig
    • 1
    • 2
    Email author
  • Muhammad Sohail
    • 3
  • Ali Asghar Mirjat
    • 4
  • Muhammad Naveed
    • 3
  • Fatima Majeed
    • 4
  • Faisal Raza
    • 5
  • Muhammad Asim Farooq
    • 5
  • Reyaj Mikrani
    • 5
  • Salman Khan
    • 6
  • Muhammad Abbas
    • 6
  • Sana Ullah
    • 6
  • Muhammad Hasnat
    • 5
  • Wen Chunxia
    • 6
  • Ghulam Jilany Khan
    • 7
  • Muhammad Tayyab Ansari
    • 2
  1. 1.State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical EngineeringNanjing UniversityNanjingChina
  2. 2.Department of Pharmaceutical Chemistry, Faculty of PharmacyBahauddin Zakariya UniversityMultanPakistan
  3. 3.School of PharmacyNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.School of Public HealthNanjing Medical UniversityNanjingPeople’s Republic of China
  5. 5.State Key Laboratory of Natural Medicines, Department of PharmaceuticsChina Pharmaceutical UniversityNanjingChina
  6. 6.School of Life Sciences, State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingChina
  7. 7.Faculty of PharmacyUniversity of Central PunjabLahorePakistan

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