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.
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References
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 43:5–17. https://doi.org/10.1016/j.currproblcancer.2018.08.003
Ahmed S, Govender T, Khan I, Rehman NU, Ali W, Shah SMH, Khan S, Hussain Z, Ullah R, Alsaid MS (2018) Experimental and molecular modeling approach to optimize suitable polymers for fabrication of stable fluticasone nanoparticles with enhanced dissolution and antimicrobial activity. Drug Des Dev Ther 12:255–269. https://doi.org/10.2147/dddt.s148912
Anandalakshmi K, Venugobal J, Ramasamy V (2016) Characterization of silver nanoparticles by green synthesis method using Pedalium murex leaf extract and their antibacterial activity. Appl Nanosci 6:399–408. https://doi.org/10.1007/s13204-015-0449-z
Asadi A (2014) Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment. Appl Nanosci 4:455–460. https://doi.org/10.1007/s13204-013-0219-8
Babar DG, Sarkar S (2017) Self-assembled nanotubes from single fluorescent amino acid. Appl Nanosci 7:101–107. https://doi.org/10.1007/s13204-017-0551-5
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 97:1250–1258. https://doi.org/10.1016/j.biopha.2017.11.059
Baig MMFA, Naveed M, Abbas M, Chunxia W, Ullah S, Hasnat M, Shad A, Muhammad S, Jilany Khan G, Tayyab Ansari M (2019a) DNA scaffold nanoparticles coated with HPMC/EC for oral delivery. Int J Pharm 562:321–332. https://doi.org/10.1016/j.ijpharm.2019.03.054
Baig MMFA, Naveed M, Abbas M, Kassim SA, Sohail M, Ullah S, Younis MR, Nawaz W, Khan GJ, Ansari MT (2019b) Evaluation of chitosan/eudragit hybrid coating over cubic DNA nanospheres with superior stability and therapeutic outcomes. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2019.05.023
Baig MMFA, Abbas M, Naveed M, Kassim SA, Khan GJ, Sohail M, Ullah S, Hasnat M, Shah K, Ansari MT (2019c) Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug. J Food Drug Anal. https://doi.org/10.1016/j.jfda.2019.03.004
Baig MMFA, Naveed M, Abbas M, Kassim SA, Khan GJ, Ullah S, Sohail M, Nawaz W, Younis MR, Ansari MT (2019d) Chitosan-coated rectangular DNA nanospheres for better outcomes of anti-diabetic drug. J Nanoparticle Res 21:98. https://doi.org/10.1007/s11051-019-4534-1
Chatterjee S, Khunti K, Davies MJ (2017) Type 2 diabetes. Lancet 389:2239–2251. https://doi.org/10.1016/S0140-6736(17)30058-2
Dave V, Sharma S, Yadav RB, Agarwal U (2017) Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis. Appl Nanosci 7:973–987. https://doi.org/10.1007/s13204-017-0634-3
Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705. https://doi.org/10.1016/S0140-6736(06)69705-5
Fisman EZ, Tenenbaum A (2015) Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes. Cardiovasc Diabetol. https://doi.org/10.1186/s12933-015-0294-0
Gangurde AB, Kundaikar HS, Javeer SD, Jaiswar DR, Degani MS, Amin PD (2015) Enhanced solubility and dissolution of curcumin by a hydrophilic polymer solid dispersion and its insilico molecular modeling studies. J Drug Deliv Sci Technol 29:226–237. https://doi.org/10.1016/j.jddst.2015.08.005
He YL (2012) Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin Pharmacokinet 51:147–162. https://doi.org/10.2165/11598080-000000000-00000
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 97:255–263. https://doi.org/10.1016/j.biopha.2017.10.101
Khan GJ, Sun L, Abbas M, Naveed M, Jamshaid T, Baig MMFA, Yuan S (2019) In-vitro pre-treatment of cancer cells with TGF-B1: A novel approach of Tail vein lung cancer metastasis mouse model for anti-metastatic studies. Curr Mol Pharmacol. https://doi.org/10.2174/1874467212666190306165703
Kim W, Egan JM (2008) The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev 60:470–512. https://doi.org/10.1124/pr.108.000604
Landfester K (2009) Miniemulsion polymerization and the structure of polymer and hybrid nanoparticles. Angew Chemie Int Ed 48:4488–4508. https://doi.org/10.1002/anie.200900723
Lopez-Gomollon S, Nicolas FE (2013) Purification of DNA oligos by denaturing polyacrylamide gel electrophoresis (PAGE). Methods Enzymol 529:65–83. https://doi.org/10.1016/B978-0-12-418687-3.00006-9
Mann A, Richa R, Ganguli M (2008) DNA condensation by poly-l-lysine at the single molecule level: role of DNA concentration and polymer length. J Control Release 125:252–262. https://doi.org/10.1016/j.jconrel.2007.10.019
Mao S, Sun W, Kissel T (2010) Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev 62:12–27. https://doi.org/10.1016/j.addr.2009.08.004
Nakayama Y, Yamaguchi H, Einaga N, Esumi M (2016) Pitfalls of DNA quantification using DNA-Binding Fluorescent Dyes and Suggested Solutions. PloS One. https://doi.org/10.1371/journal.pone.0150528
Naveed M, Phil L, Sohail M, Hasnat M, Baig MMFA, Ihsan AU, Shumzaid M, Kakar MU, Mehmood Khan T, Akabar MD, Hussain MI, Zhou QG (2019) Chitosan oligosaccharide (COS): An overview. Int J Biol Macromol 129:827–843. https://doi.org/10.1016/j.ijbiomac.2019.01.192
Olokoba AB, Obateru OA, Olokoba LB (2012) Type 2 diabetes mellitus: a review of current trends. Oman Med J 27:269–273. https://doi.org/10.5001/omj.2012.68
Sansukcharearnpon A, Wanichwecharungruang S, Leepipatpaiboon N, Kerdcharoen T, Arayachukeat S (2010) High loading fragrance encapsulation based on a polymer-blend: preparation and release behavior. Int J Pharm 391:267–273. https://doi.org/10.1016/j.ijpharm.2010.02.020
Scheen AJ (2018) The safety of gliptins: updated data in 2018. Expert Opin Drug Saf 17(2018):387–405. https://doi.org/10.1080/14740338.2018.1444027
Swisa A, Glaser B, Dor Y (2017) Metabolic stress and compromised identity of pancreatic beta cells. Front Genet. https://doi.org/10.3389/fgene.2017.00021
Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL (2010) Conversion of adult pancreatic α-cells to Β-cells after extreme Β-cell loss. Nature 464:1149–1154. https://doi.org/10.1038/nature08894
Velmurugan R, Selvamuthukumar S (2016) Development and optimization of ifosfamide nanostructured lipid carriers for oral delivery using response surface methodology. Appl Nanosci 6:159–173. https://doi.org/10.1007/s13204-015-0434-6
Yue S, Song X, Song W, Bi S (2019) An enzyme-free molecular catalytic device: dynamically self-assembled DNA dendrimers for in situ imaging of microRNAs in live cells. Chem Sci 10:1651–1658. https://doi.org/10.1039/c8sc04756a
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.
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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.
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Baig, M.M.F.A., Sohail, M., Mirjat, A.A. et al. PLL-alginate and the HPMC-EC hybrid coating over the 3D DNA nanocubes as compact nanoparticles for oral administration. Appl Nanosci 9, 2105–2115 (2019). https://doi.org/10.1007/s13204-019-01075-5
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DOI: https://doi.org/10.1007/s13204-019-01075-5