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Modified Physicochemical Properties of Acidic Model Drugs Immobilized on Fe3O4Magnetic Iron Oxide Nanoparticles

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Pharmaceutical Chemistry Journal Aims and scope

Nanoparticles are now extensively evaluated as drug carriers. The main objective of the present work was to evaluate the difference in physicochemical properties (solubility, permeability, lipophilicity) between acidic drugs immobilized on magnetic iron oxide nanoparticles and the same drugs in their unbound form. Synthesis of Fe3O4 magnetic iron oxide nanoparticles coated with (3-aminopropyl)triethoxysilane (APTES) was carried out with the chosen drugs attached. The obtained nanostructures were characterized using IR spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM) and dynamic light scattering (DLS) techniques, and physicochemical properties of the immobilized drugs were studied. The drug solubility was measured using the saturation shake-flask method. The permeability was measured using dialysis membranes, MWCO 50 kD with pores <10 nm. The lipophilicity was measured by partitioning in octanol. The drugs showed excellent solubility and permeability at low pH values (pH 2.0 and 5.0) and low solubility and permeability at higher pH values (pH 6.5 and 7.5) in comparison to the corresponding unbound drugs. The MNP[APTES]-immobilized drugs diffused to the organic phase very poorly, even in their non-ionized form (pH 2.0) and showed extremely low distribution coefficients. It was concluded that the immobilization of drugs on MNP[APTES] particles strongly modifies their physicochemical properties such as solubility, permeability and lipophilicity. This circumstance should be taken into account in designing new drug delivery systems, as the immobilization may strongly influence passive absorption. Extremely high release and dissolution rates of the tested drugs, followed by their efficient permeability through membrane pores at low pH, is the reason why the oral administration of therapeutic agents immobilized on MNPs should be considered as a method for more efficient drug delivery.

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References

  1. J. Dobson, Drug Develop. Res., 67(1), 55 – 60 (2006).

    Article  CAS  Google Scholar 

  2. C. Sun, J. S. H. Lee, and M. Zhang, Adv. Drug Delivery Rev., 60(11), 1252 – 1265 (2008).

    Article  CAS  Google Scholar 

  3. M. Colombo, S. Carregal-Romero, M. F. Casula, et al., Chem. Soc. Rev., 41, 4306 – 4334 (2012).

    Article  CAS  Google Scholar 

  4. D. A. Hume, I. L. Ross, S. R. Himes, et al., J. Leukocyte Biol., 72, 621 – 627 (2002).

    CAS  PubMed  Google Scholar 

  5. N. Chiannilkulchai, Z. Driouich, J. P. Benoit, et al, Sel. Cancer Ther., 5(1), 1 – 11 (1989).

    Article  CAS  Google Scholar 

  6. H. Pinto-Alphandary, A. Andremont, and P. Couvreur, Int. J. Antimicrob. Agents, 13 (3), 155 – 168 (2000).

    Article  CAS  Google Scholar 

  7. A.Wicki, D.Witzigmann, V. Balasubramanian, and J. Huwyler, J. Control. Release, 200, 138 – 157 (2015).

    Article  CAS  Google Scholar 

  8. N. Kohler, G. E. Fryxell, and M. Zhang, J. Am. Chem. Soc., 126(23), 7206 – 7211 (2004).

    Article  CAS  Google Scholar 

  9. T. Shen, R. Weissleder, M. Papisov, et al, Magn. Reson. Med., 29(5), 599 – 604 (1993).

    Article  CAS  Google Scholar 

  10. K. M. Ho and P. Li, Langmuir, 24, 1801 – 1807 (2008).

    Article  CAS  Google Scholar 

  11. X. Shen, X. Fang, Y. Zhou, and H. Liang, Chem. Lett., 33(11), 1468 – 1469 (2004).

    Article  CAS  Google Scholar 

  12. R. Hao, R. Xing, Z. Xu, et al., Adv. Mater., 22(25), 2729 – 2742 (2010).

    Article  CAS  Google Scholar 

  13. S. Mornet, S. Vasseur, F. Grasset, and E. Diguet, J. Mater. Chem., 14, 2161 – 2175 (2004).

    Article  CAS  Google Scholar 

  14. O. Veiseh, J. W. Gunn, and M. Zhang, Adv. Drug Delivery Rev., 62, 284 – 304 (2010).

    Article  CAS  Google Scholar 

  15. K. C. Barick, S. Singh, N. V. Jadhav, et al., Adv. Funct. Mater., 22(23), 4975 – 4984 (2012).

    Article  CAS  Google Scholar 

  16. J. Nowak-Jary, A. Defort, J. J. Kozio3, Micro Nano Lett., 12(3), 170 – 174 (2017).

  17. J. Nowak-Jary, E. Gronczewska, W. Worobiec, Pharm. Chem. J., 51(11), 985 – 994 (2017).

    Article  Google Scholar 

  18. J. Nowak-Jary and J. J. Kozio3, Micro Nano Lett., 13(3), 316 – 320 (2018).

  19. M. Ma, Y. Zhang, W. Yu, et al., Colloid Surf. A., 212(2–3), 219 – 226 (2003).

    Article  CAS  Google Scholar 

  20. R. Massart, IEEE Trans. Magn., 17(2), 1247 – 1248 (1981).

    Article  Google Scholar 

  21. H. Cao, J. He, L. Deng, and X. Gao, Appl. Surf. Sci., 255(18), 7974 – 7980 (2009).

    Article  CAS  Google Scholar 

  22. D. J. W. Grant and T. Higuchi. Solubility Behavior of OrganicCompounds, New York: John Wiley & Sons (1990).

    Google Scholar 

  23. S. H. Yalkowsky, S. Banerjee, Aqueous Solubility: Methods of Estimation for Organic Compounds, New York: Marcel Dekker (1992).

    Google Scholar 

  24. J. C. Dearden and G. M. Bresnen, Quant. Struct.-Act. Relat., 7(3), 133 – 144 (1988).

    Article  CAS  Google Scholar 

  25. A. Hersey, A. P. Hill, R. M. Hyde, and D. J. Livingstone, Quan.t Struct.-Act. Relat, 8(4), 288 – 296 (1989).

    Article  CAS  Google Scholar 

  26. R. G. Halliday, A. L. Drasco, C. E. Lumley, and S. R. Walker, Res. Dev. Menage., 27, 63 – 77 (1997).

    Google Scholar 

  27. G. Gaviraghi, R. J. Barnaby, and M. Pellegatti, in: Pharmacokinetic Optimization in Drug Research: Pharmacokinetic Challenges in Lead Optimization, B. Testa, H. van de Waterbeemd, G. Folkers, R. Guy (eds), Weinheim:Verlag Helvetica Chimica Acta – Wiley-VCH (2001), pp. 3 – 14.

  28. C. A. Lipiñski, F. Lombardo, B. W. Dominy, and P. J. Feeney, Adv. Drug Delivery Rev., 46(1–3), 3 – 26 (2001).

    Article  Google Scholar 

  29. G. L. Amidon, H. Lennernäs, V. P. Shah, J. R. Crison, Pharm. Res., 12(3), 413 – 420 (1995).

    Article  CAS  Google Scholar 

  30. G. L. Amidon, in: Biopharmaceutics Drugs Classification and International Drug Regulation: The Rationale for a Biopharmaceutics Drug Classification, Capsugel Library (1995) pp. 179 – 194.

  31. G. L. Amidon, C. R. Waalgreen, in: Biopharmaceutics Drug Classification and International Drug Regulation: Rationale and Implementation of a Biopharmaceutics Classification System (BCS) for New Drug Regulation, Capsugel Library (1998), pp. 13 – 27.

  32. A. S. Hussain, Methods for Permeability Determination: A Regulatory Perspective, AAPS Workshop on Permeability Definitions and Regulatory Standards for Bioequivalence, Arlington, 17 – 19 August (1998).

  33. CPMP Note for Guidance on the Investigation of Bioavailability and Bioequivalence. (CPMP / EWP / QWP / 1401 / 98 Draft), December 1998.

  34. FDA Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties / Active Ingredients Based on a Biopharmaceutics Classification System, CDERGUID / 2062dft.wpd Draft, January 1999.

  35. A. Avdeef, K. J. Box, J. E. A. Comer, et al, Pharm. Res., 15(2), 209 – 215 (1998).

    Article  CAS  Google Scholar 

  36. A. Avdeef, D. A. Barret, P. N. Shaw, et al, J. Med. Chem., 39(22), 4377 – 4381 (1996).

    Article  CAS  Google Scholar 

  37. L. H. Reddy, J. L. Arias, J. Nicolas, and P. Couvreur, Chem. Rev., 112(11), 5818 – 5878 (2012).

    Article  CAS  Google Scholar 

  38. E. K. Schlachter, H. R. Widmer, A. Bregy, et al, Int. J. Nanomed., 6, 1793 – 1800 (2011).

    CAS  Google Scholar 

  39. A. Hanini, A. Schmitt, K. Kacem, et al., Int. J. Nanomed., 6, 787 – 794 (2001).

    Google Scholar 

  40. M. Barzegar-Jalali, K. Adibkia, H. Valizadeh, et al, J. Pharm. Pharm. Sci., 11(1), 167 – 177 (2008).

    Article  CAS  Google Scholar 

  41. L. Xie, S. Beyer, V. Vogel, et al, Int. J. Pharm., 488(1–2), 108 – 119 (2015).

    Article  CAS  Google Scholar 

  42. Y. Zhou, C. He, K. Chen, et al, J. Control. Release, 243, 11 – 20 (2016).

    Article  CAS  Google Scholar 

Download references

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Nowak-Jary, J., Defort, A. & Kozioƚ, J.J. Modified Physicochemical Properties of Acidic Model Drugs Immobilized on Fe3O4Magnetic Iron Oxide Nanoparticles. Pharm Chem J 53, 1025–1035 (2020). https://doi.org/10.1007/s11094-020-02118-w

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