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A comparative study on effect of metformin and metformin-conjugated nanotubes on blood glucose homeostasis in diabetic rats

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Abstract

Diabetes mellitus is one of the most prevalent metabolic disorders. Carbon nanotubes have the advantage to cross the plasma membrane without damaging the cells, improving the biological effect of a drug and reducing its side effects. In the present study, the effect of metformin and metformin-conjugated nanotubes was investigated on blood glucose level in the streptozotocin-induced male diabetic rats. Diabetes in the animals was induced with a single dose of streptozotocin (60 mg/kg; i.p.) and after 3 days the blood glucose was analyzed. Animals showing fasting blood glucose higher than 250 mg/dL were considered as diabetic rats. The animals were treated with metformin and metformin-conjugated nanotubes (150 mg/kg; p.o.) daily and every 48-h for 1 week. Changes in animals’ serum blood glucose level were evaluated daily during the treatment period. The results of this study showed that metformin reduced blood glucose levels in diabetic animals. Metformin-conjugated nanotubes significantly reduced the blood glucose levels in diabetic rats (p < 0.01). There was no significant difference in blood glucose level between metformin and metformin-conjugated nanotubes groups (p > 0.05). However, when both formulations of metformin were administered every 48-h, metformin-conjugated nanotubes reduced glycaemia for a longer time than metformin alone (p < 0.001). This study showed that the metformin-conjugated nanotubes would be able to reduce the blood glucose, prolong drug delivery and efficacy duration in animals which were treated with metformin-conjugated nanotubes compared with metformin alone.

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References

  • Amorim MJ, Ferreira JP (2001) Microparticles for delivering therapeutic peptides and proteins to the lumen of the small intestine. Eur J Pharm Biopharm 52:39–44

    Article  CAS  PubMed  Google Scholar 

  • Bianco A, Kostarelos K, Prato M (2005) Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol 9:674–679

    Article  CAS  PubMed  Google Scholar 

  • Bilous R, Donnelly R (2010) Handbook of diabetes, 4th edn. Blackwell science, UK

    Book  Google Scholar 

  • Cetin M, Atila A, Sahin S, Vural I (2013) Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA nanoparticles. Pharm Dev Technol 18:570–576

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Chen S, Zhao X, Kuznetsova LV, Wong SS, Ojima I (2008) Functionalized single-walled carbon nanotubes as rationally designed vehicles for tumor-targeted drug delivery. J Am Chem Soc 130:16778–16785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen G, He Y, Wu X, Zhang Y, Luo C, Jing P (2012) In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer. Braz J Med Biol Res 45(8):771–776

    Article  PubMed Central  PubMed  Google Scholar 

  • Cheng JT, Huang CC, Liu IM, Tzeng TF, Chang CJ (2006) Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats. Diabetes 55:819–825

    Article  CAS  PubMed  Google Scholar 

  • Corti G, Cirri M, Maestrelli F, Mennini N, Mura P (2008) Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm 68:303–309

    Article  CAS  PubMed  Google Scholar 

  • Davidson MB, Peters AL (1997) An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 102(1):99–110

    Article  CAS  PubMed  Google Scholar 

  • Douglas SM, Chou JJ, Shih WM (2007) DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc Natl Acad Sci USA 104:6644–6648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • El-Atat F, McFarlane SI, Sowers JR (2004) Diabetes, hypertension, and cardiovascular derangements: pathophysiology and management. Curr Hypertens 6:215–223

    Article  Google Scholar 

  • Feazell RP, Nakayama-Ratchford N, Dai H, Lippard SJ (2007) Soluble single-walled carbon nanotubes as longboat delivery systems for platinum (IV) anticancer drug design. J Am Chem Soc 129:8438–8439

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fu K, Huang W, Lin Y, Riddle LA, Carroll DL, Sun YP (2001) Defunctionalization of functionalized carbon nanotubes. Nano Lett 1(8):439–441

    Article  CAS  Google Scholar 

  • Galindo-Rodriguez SA, Allemann E, Fessi H, Doelker E (2005) Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit Rev Ther Drug Carrier Syst 22:419–464

    Article  CAS  PubMed  Google Scholar 

  • Gelperina S, Kisich K, Iseman MD, Heifets L (2005) The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. Am J Respir Crit Care Med 172:1487–1490

    Article  PubMed Central  PubMed  Google Scholar 

  • Hundal RS, Inzucchi SE (2003) Metformin: new understandings, new uses. Drugs 63:1879–1894

    Article  CAS  PubMed  Google Scholar 

  • Khazaei A, Rad MN, Borazjani MK (2010) Organic functionalization of single-walled carbon nanotube with some chemotherapeutic agents as a potential method for drug delivery. Int J Nanomed 5:639–645

    Article  CAS  Google Scholar 

  • Kim WJ, Kang SO, Ah CS, Lee YW, Ha DH, Choi IS, Yun WS (2004) Functionalization of shortened SWCNTs using esterification. Bull Korean Chem Soc 25:1301–1302

    Article  CAS  Google Scholar 

  • Kumar SP, Prathibha D, Shankar NLG, Parthibarajan R, Mastyagiri L, Shankar M (2012) Pharmaceutical application of carbon nanotube-mediated drug delivery system. Int J Pharm Sci Nanotechnol 5:1685–1696

    Google Scholar 

  • Liu Z, Sun X, Nakayama-Ratchford N, Dai H (2007) Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 1:50–56

    Article  PubMed  Google Scholar 

  • Liu Z, Davis C, Cai W, He L, Chen X, Dai H (2008) Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc Natl Acad Sci USA 105:1410–1415

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu H, He J, Tang J, Liu H, Pang P, Cao D et al (2010) Translocation of single-stranded DNA through single-walled carbon nanotubes. Science 327:64–67

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marathe PH, Wen Y, Norton J, Greene DS, Barbhaiya RH, Wilding IR (2000) Effect of altered gastric emptying and gastrointestinal motility on metformin absorption. Br J Clin Pharmacol 50:325–332

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marshall MW, Popa-Nita S, Shapter JG (2006) Measurement of functionalised carbon nanotube carboxylic acid groups using a simple chemical process. Carbon 44:1137–1141

    Article  CAS  Google Scholar 

  • Momoh MA, Kenechukwu FC, Attama AA (2013) Formulation and evaluation of novel solid lipid microparticles as a sustained release system for the delivery of metformin hydrochloride. Drug Deliv 20(3–4):102–111

    Article  CAS  PubMed  Google Scholar 

  • Muller J, Delos M, Panin N, Rabolli V, Huaux F, Lison D (2009) Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat. Toxicol Sci 110:442–448

    Article  CAS  PubMed  Google Scholar 

  • Niyogi S, Hamon MA, Hu H, Zhao B, Bhowmik P, Sen R, Itkis ME, Haddon RC (2002) Chemistry of single-walled carbon nanotubes. Acc Chem Res 35:1105–1113

    Article  CAS  PubMed  Google Scholar 

  • Pantarotto D, Briand JP, Prato M, Bianco A (2004) Translocation of bioactive peptides across cell membranes by carbon nanotubes. Chem Commun 7(1):16–17

    Article  Google Scholar 

  • Piao J, Lee JE, Weon KY, Kim DW, Lee JS, Park JD et al (2009) Development of novel mucoadhesive pellets of metformin hydrochloride. Arch Pharm Res 32:391–397

    Article  CAS  PubMed  Google Scholar 

  • Pompeo F, Resasco DE (2002) Water solubilization of single-walled carbon nanotubes by functionalization with glucosamine. Nano Lett 2:369–373

    Article  CAS  Google Scholar 

  • Tripisciano C, Kraemer K, Taylor A, Borowiak-Palen E (2009) Single-wall carbon nanotubes based anticancer drug delivery system. Chem Phys Lett 478:200–205

    Article  CAS  Google Scholar 

  • Wang H, Wang J, Deng X, Sun H, Shi Z, Gu Z, Liu Y, Zhao Y (2004) Biodistribution of carbon single-wall carbon nanotubes in mice. J Nanosci Nanotechnol 4(8):1019–1024

    Article  CAS  PubMed  Google Scholar 

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The authors report no conflicts of interest in this work.

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Science, Bu-Ali Sina University, Hamedan, Iran

    Naser Mirazi & Abdolkarim Hosseini

  2. Department of Biology, Faculty of Basic Science, Hamedan Islamic Azad University, Hamedan, Iran

    Jamileh Shoaei

  3. Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran

    Ardeshir Khazaei

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  1. Naser Mirazi
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  2. Jamileh Shoaei
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  3. Ardeshir Khazaei
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  4. Abdolkarim Hosseini
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Correspondence to Naser Mirazi.

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Mirazi, N., Shoaei, J., Khazaei, A. et al. A comparative study on effect of metformin and metformin-conjugated nanotubes on blood glucose homeostasis in diabetic rats. Eur J Drug Metab Pharmacokinet 40, 343–348 (2015). https://doi.org/10.1007/s13318-014-0213-x

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  • DOI: https://doi.org/10.1007/s13318-014-0213-x

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