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Metformin-Loaded BSA Nanoparticles in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug

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Abstract

Clinical and experimental data suggest that there is a strong association between type II diabetic mellitus and pancreatic cancer. The present study focuses on exploring the anticancer and antidiabetic properties of metformin-loaded bovine serum albumin nanoparticles (BSA NPs) on (MiaPaCa-2) pancreatic carcinoma cell lines. Albumin nanoparticles were synthesized using coacervation method and the average size of the particles was found to be 97 nm. The particles were stable and showed a spherical morphology with narrow size distribution. We investigated the impact of two stages characterized in type II diabetes mellitus (hyperglycemia and hyperinsulinemia) on the proliferation of MiaPaCa-2 cells and compared the inhibitory effects of bare metformin to that of MET-BSA NPs. Further, different concentrations of insulin and glucose were added along with bare metformin, bare BSA, and metformin encapsulated BSA carrier on MiaPaCa-2 cells to check the strong association between type II diabetes and pancreatic cancer. The results revealed that MET-BSA NPs showed more toxicity when compared with drug and carrier individually.

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References

  1. Nie, S. M., Xing, Y., Kim, G. J., & Simons, J. W. (2007). Nanotechnology applications in cancer. Annual Review of Biomedical Engineering, 9, 257–288.

    Article  CAS  PubMed  Google Scholar 

  2. Nasongkla, N., Bey, E., Ren, J. M., Ai, H., Khemtong, C., Guthi, J. S., et al. (2006). Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Letters, 6, 2427–2430.

    Article  CAS  PubMed  Google Scholar 

  3. Jiang, W., Kim, B. Y. S., Rutka, J. T., & Chan, W. C. W. (2008). Nanoparticle-mediated cellular response is size-dependent. Nature Nanotechnology, 3, 145–150.

    Article  CAS  PubMed  Google Scholar 

  4. Chithrani, B. D., Ghazani, A. A., & Chan, W. C. W. (2006). Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Letters, 6, 662–668.

    Article  CAS  PubMed  Google Scholar 

  5. Belting, M., Sandgren, S., & Wittrup, A. (2005). Nuclear delivery of macromolecules: barriers and carriers. Advanced Drug Delivery Reviews, 57, 505–527.

    Article  CAS  PubMed  Google Scholar 

  6. Manju, R., Deependra, S., Saraf, S., & Swarnalata, S. (2006). Nanocarriers: Promising vehicle for bioactive drugs. Bioogical & Pharmaceutical Bulletin, 29(9), 1790–1798.

    Article  Google Scholar 

  7. Douglas, T., & Young, M. (1998). Host–guest encapsulation of materials by assembled virus protein cages. Nature, 393, 152–155.

    Article  CAS  Google Scholar 

  8. Comellas, A. M., Engelkamp, H., Claessen, V. I., Sommerdijk, N. A. J. M., & Rowan, A. E. (2007). A virus-based single-enzyme nanoreactor. Nature Nanotechnology, 2, 635–639.

    Article  Google Scholar 

  9. Christie, R. J., & Grainger, D. W. (2003). Design strategies to improve soluble macromolecular delivery constructs. Advanced Drug Delivery Reviews, 55, 421–437.

    Article  CAS  PubMed  Google Scholar 

  10. Rajendran, L., Knolker, H. J., & Simons, K. (2010). Subcellular targeting strategies for drug design and delivery. Nature Reviews Drug Discovery, 9, 29–42.

    Article  CAS  PubMed  Google Scholar 

  11. Byrne, J. D., Betancourt, T., & Brannon, P. L. (2008). Active targeting schemes for nanoparticle systems in cancer therapeutics. Advanced Drug Delivery Reviews, 60, 1615–1626.

    Article  CAS  PubMed  Google Scholar 

  12. Kratz, F., Beyer, U., & Schutte, M. T. (1999). Drug-polymer conjugates containing acid-cleavable bonds. Critical Reviews in Therapeutic Drug Carrier Systems, 16, 245–288.

    Article  CAS  PubMed  Google Scholar 

  13. Uchida, M., Klem, M. T., Allen, M., Suci, P., Flenniken, M., Gillitzer, E., et al. (2007). Biological containers: Protein cages as multifunctional nanoplatforms. Advanced Materials, 19, 1025–1042.

    Article  CAS  Google Scholar 

  14. Manchester, M., & Singh, P. (2006). Virus-based nanoparticles (VNPs): Platform technologies for diagnostic imaging. Advanced Drug Delivery Reviews, 58, 1505–1522.

    Article  CAS  PubMed  Google Scholar 

  15. Langer, K., Balthasar, S., Vogel, V., Dinauer, N., Von, B. H., & Schubert, D. (2003). Optimization of the preparation process for human serum albumin (HSA) nanoparticles. International Journal of Pharmaceutics, 257, 169–180.

    Article  CAS  PubMed  Google Scholar 

  16. Müller, G. M., Leuenberger, H., & Kissel, T. (1996). Albumin nanospheres as carriers for passive drug targeting: An optimized manufacturing technique. Pharmaceutical Research, 13, 32–37.

    Article  PubMed  Google Scholar 

  17. Amit, D., Chitra, R., Choudhry, R. R., & Ramanadham, M. (2004). Structural changes during the unfolding of Bovine serum albumin in the presence of urea: A small angle neutron scattering study. Pramana Journal of Physics, 63(2), 363–368.

    Article  Google Scholar 

  18. Steenkamp, P. A., & Coetzee, P. P. (1993). Simultaneous determination of toxic heavy metals in Metformin hydrochloride using reversed-phase high-performance liquid chromatography. Fresenius’ Journal of Analalytical Chemistry, 346, 1017–1021.

    Article  CAS  Google Scholar 

  19. Miller, R. A., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013). Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature, 3494, 256–260.

    Article  Google Scholar 

  20. Ledford, H. (2010). Diabetes drugs offered fresh start. Nature, 466, 420–421.

    Article  PubMed  Google Scholar 

  21. Bailey, C. J., Wilcock, C., & Day, C. (1992). Effect of metformin on glucose metabolism in the splanchnic bed. British Journal of Pharmacology, 105, 1009–1013.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Bell, G. I., & Polonsky, K. S. (2001). Diabetes mellitus and genetically programmed defects in beta-cell function. Nature, 414, 788–791.

    Article  CAS  PubMed  Google Scholar 

  23. Jolien, D. J., Adriaan, K., Philippe, L., Michiel., G. W., Jan., V. D. K, Daniel. B., et al. (2010). Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. British Medical Journal, 340, c2181:1–7.

  24. Prizment, A. E., Gross, M., Rasmussen, T., Peacock, J. M., & Anderson, K. E. (2012). Genes related to diabetes may be associated with pancreatic cancer in a population-based case–control study in Minnesota. Pancreas, 41(1), 50–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Susan, M. G., Peter, H. G., William, L., Kiang, L., Laura, C., & Alan, D. (2000). Abnormal glucose metabolism and pancreatic cancer mortality. Journal of American Medical Association, 283(19), 2552–2558.

    Article  Google Scholar 

  26. Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Janna, K. D., et al. (2011). Clinical pharmacokinetics of metformin. Clinical Pharmacokinetics, 50, 81–98.

    Article  CAS  PubMed  Google Scholar 

  27. Mohanty, B., Aswal, V. K., Kohlbrecher, J., & Bohidar, H. B. (2005). Synthesis of gelatin nanoparticles via simple coacervation. Journal of Surface Science Technology, 21, 149–160.

    CAS  Google Scholar 

  28. Shinde, U. A., & Nagarsenker, M. S. (2009). Characterization of gelatin–sodium alginate complex coacervation system. Indian Journal of Pharmaceutical Sciences, 71, 313–317.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Scarpello, J.H.B. (2003). Improving survival with metformin: The evidence base today. Diabetes Metabolism, 29, 6S36–6S43.

  30. Sharon, A. O. T., Brian, L. S., Eamon, P. J., Noreen, C. G., Misaho, Y., & John, B. (2003). The MTS assay as an indicator of chemo sensitivity/resistance in malignant gynaecological tumours. Cancer Detection and Prevention, 27, 47–54.

    Article  Google Scholar 

  31. Ferrari, M. (2005). Cancer nanotechnology: Opportunities and challenges. Nature Reviews Cancer, 5, 161–171.

    Article  CAS  PubMed  Google Scholar 

  32. Wolfgang, A. D., Julla, S., Dletmer, P. B., Ronald, M., & Heinz, H. F. (1995). Development of propidium iodide fluorescence assay for proliferation and cytotoxicity assays. Anti-Cancer Drugs, 6, 522–532.

    Article  Google Scholar 

  33. Singh, R., & Lillard, J. W. (2009). Nanoparticle-based targeted drug delivery. Experimental and Molecular Pathology, 86, 215-213.

    Article  Google Scholar 

  34. Doshi, N. & Mitragotri, S. (2009). Designer biomaterials for nanomedicine. Advanced Functional Materials, 19, 3843.

  35. Luginbuehl, V., Meinel, L., Merkle, H. P., & Gander, B. B. (2004). Localized delivery of growth factors for bone repair. European Journal of Pharmaceutics and Biopharmaceutics, 58, 197–208.

    Article  CAS  PubMed  Google Scholar 

  36. Roser, M., Fischer, D., & Kissel, T. (1998). Surface-modified bio de-gradable albumin nano- and microspheres. II: Effect of surface charges on in vitro phagocytosis and biodistribution in rats. European Journal of Pharmaceutics and Biopharmaceutics, 46, 255–263.

    Article  CAS  PubMed  Google Scholar 

  37. Moghimi, S. M., Hunter, A. C., & Murray, J. C. (2011). Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacological Reviews, 53, 283–318.

    Google Scholar 

  38. Kaushelendra, M., Himesh, S., Govind, N., Sita, S. P., & Singhai, A. K. (2011). Method development and validation of metformin hydrochloride in tablet dosage form. European Journal of Chemistry, 8, 1309–1313.

    Google Scholar 

  39. Yan, J. H., Yi, L., & Xiao, H. X. (2009). Investigation of the interaction between berberine and human serum albumin. Biomacromolecules, 10, 517–521.

    Article  Google Scholar 

  40. Xing, J. G., Xiu, D. S., & Shu, K. X. (2009). Spectroscopic investigation of the interaction between riboflavin and bovine serum albumin. Journal of Molecular Structure, 931, 55–59.

    Article  Google Scholar 

  41. Jee, S. H., Ohrr, H., Sull, J. W., Yun, J. E., Min, J., & Jonathan, M. S. (2005). Fasting serum glucose level and cancer risk in Korean men and women. Journal of American Medical Association, 293, 194–202.

    Article  CAS  Google Scholar 

  42. Pannala, R., Basu, A., Petersen, G. M., & Chari, S. T. (2009). New-onset diabetes: A potential clue to the early diagnosis of pancreatic cancer. Lancet Oncology, 10, 88–95.

    Article  Google Scholar 

  43. Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R. (2009). Diabetes and cancer. Endocrine Related Cancer, 16, 1103–1123.

    Article  CAS  PubMed  Google Scholar 

  44. Giovannucci, E., & Michaud, D. (2007). The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology, 132, 2208–2225.

    Article  CAS  PubMed  Google Scholar 

  45. Issam, B. S., Yannick, L. M. B., Jean, F. T., & Frederck, T. (2010). Metformin in cancer therapy: A new perspective for an old antidiabetic drug? Molecular Cancer Therapeutics, 9(5), 1092–1099.

    Article  Google Scholar 

  46. Enrique, R., James, S., & Krisztina, K. (2010). Crosstalk between insulin/insulin-like growth factor-1 receptors and g protein-coupled receptor signaling systems: A novel target for the antidiabetic drug metformin in pancreatic cancer. Clinical Cancer Research, 16(9), 2505–2511.

    Article  Google Scholar 

  47. Dunyaporn, T., Yan, Z., Hue, Z., Yusuke, D., Zhao, C., Helene, P., et al. (2006). Cancer Cell, 10, 241–252.

    Article  Google Scholar 

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Acknowledgments

Authors would like to acknowledge Department of Science and Technology for providing the external funding to carry out the project entitled, “Biocompatibility of surface modified and unmodified Graphene oxide nanoparticles” (NO:SR/FT/LS-18/2012). We would also thank Centre for Nano Technology & Advanced Biomaterials (CeNTAB) and Centre for Advanced Research in Indian System of Medicine (CARISM), SASTRA University for providing the facilities to carry out this project.

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  1. Center for Nanotechnology and Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur, 613401, Tamilnadu, India

    Pinkybel Jose, K. Sundar, C. H. Anjali & Aswathy Ravindran

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  1. Pinkybel Jose
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Correspondence to Aswathy Ravindran.

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Jose, P., Sundar, K., Anjali, C.H. et al. Metformin-Loaded BSA Nanoparticles in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug. Cell Biochem Biophys 71, 627–636 (2015). https://doi.org/10.1007/s12013-014-0242-8

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