Skip to main content
SpringerLink
Log in

Optimization of Formulation and Process Variables for the Preparation of Novel Doxorubicin-Loaded Sonosensitive Nanodroplets

  • Original Paper
  • Published:
Journal of Cluster Science Aims and scope Submit manuscript

Abstract

In the present study the effect of process (homogenization speed) and formulation (polymer concentration, surfactant concentration, drug amount, perfluorohexane volume fraction and co-surfactant inclusion) variables on particle size, entrapment efficiency, and drug release kinetics of doxorubicin-loaded alginate stabilized perfluorohexane nanodroplets were evaluated. Particle size and doxorubicin entrapment efficiency were highly affected by formulation and process variables. In vitro release profile of doxorubicin from all formulations was an apparently biphasic release process and 7–13 % of drug released from nanodroplets after 24 h incubation in PBS, pH 7.4, depending on the nanodroplets composition but ultrasound exposure for 10 min resulted in triggered release of 85.95 % of doxorubicin fromoptimal formulation (G). The inclusion of Span 60 (0.15 %), Poloxamer 188 (0.15 %) as co-surfactants reduced the particle size of nanodroplets from 51.8 to 42.3 and 35.6 nm, respectively. The entrapment efficiency decreased for span 60, while it did not changed in the case of Poloxamer 188. Comparison of drug release kinetics demonstrated that drug release was delayed for both Span 60 and Poloxamer 188. Thus, it was concluded that the particle size, entrapment efficiency and the doxorubicin release kinetics could easily be adjusted by taking advantage of process and formulation variables.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. S. Miura, K. Tachibana, T. Okamoto, and K. Saku (2002). Biochem. Biophys. Res. Commun. 298, 587.

    Article  CAS  Google Scholar 

  2. Y. Ueno, S. Sonoda, R. Suzuki, M. Yokouchi, Y. Kawasoe, K. Tachibana, K. Maruyama, T. Sakamoto, and S. Komiya (2011). Cancer Biol. Ther. 12, 270.

    Article  CAS  Google Scholar 

  3. G. A. Husseini, D. Velluto, L. Kherbeck, W. G. Pitt, J. A. Hubbell, and D. A. Christensen (2013). Colloids Surf. B 101, 153.

    Article  CAS  Google Scholar 

  4. N. Rapoport, Z. Gao, and A. Kennedy (2007). J. Natl. Cancer Inst. 99, 1095.

    Article  CAS  Google Scholar 

  5. S. Mitragotri (2005). Nat. Rev. Drug Discov. 4, 255.

    Article  CAS  Google Scholar 

  6. N. Rapoport, D. A. Christensen, A. M. Kennedy, and K. H. Nam (2010). Ultrasound Med. Biol. 36, 419.

    Article  Google Scholar 

  7. T. O. Matsunaga, P. S. Sheeran, S. Luois, J. E. Streeter, L. B. Mullin, B. Banerjee, and P. A. Dayton (2012). Theranostics 2, 1185.

    Article  CAS  Google Scholar 

  8. O. D. Kripfgans, J. B. Fowlkes, D. L. Miller, O. P. Eldevik, and P. L. Carson (2000). Ultrasound Med. Biol. 26, 1177.

    Article  CAS  Google Scholar 

  9. P. S. Sheeran and P. A. Dayton (2012). Curr. Pharm. Des. 18, 2152.

    Article  CAS  Google Scholar 

  10. S. Hernot and A. L. Klibanov (2008). Adv. Drug Deliv. Rev. 60, 1153.

    Article  CAS  Google Scholar 

  11. R. Suzuki, T. Takizawa, Y. Negishi, K. Hagisawa, K. Tanaka, K. Sawamura, N. Utoguchi, T. Nishioka, and K. Maruyama (2007). J. Control. Release 117, 130.

    Article  CAS  Google Scholar 

  12. N. Reznik, R. Williams, and P. N. Burns (2011). Ultrasound Med. Biol. 37, 1271.

    Article  Google Scholar 

  13. H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori (2000). J. Control. Release 65, 271.

    Article  CAS  Google Scholar 

  14. C. Chretien and J. C. Chaumeil (2005). Int. J. Pharm. 304, 8.

    Article  Google Scholar 

  15. G. Jiang, S. Min, E. J. Oh, and S. K. Hahn (2007). Biotechnol. Bioprocess Eng. 12, 648.

    Google Scholar 

  16. K. Yong Lee and D. Mooney (2012). Prog. Polym. Sci. 37, 106.

    Article  Google Scholar 

  17. I. Kurt and C. Taylor (2009). J. Food Hydrocoll. 3, 1.

    Google Scholar 

  18. T. L. Bowersock, H. HogenEsch, M. Suckow, R. E. Porter, R. Jackson, and K. Park (1996). J. Control. Release 39, 209.

    Article  CAS  Google Scholar 

  19. B. Thu, P. Bruheim, T. Espevik, O. Smidsrød, P. Soon-Shiong, and G. Skjaệk-Brñk (1996). Biomaterials 17, 1031.

    Article  CAS  Google Scholar 

  20. A. J. Rebeiro, R. J. Neufeld, A. Philippe, and J. C. Chaumeil (1999). Int. J. Pharm. 187, 115.

    Article  Google Scholar 

  21. B. Sarmento, A. Ribeiro, F. Veiga, R. Neufeld, and D. Ferreira (2005). Revista Portuguesa Farmácia 2, 139.

    Google Scholar 

  22. C. Ouwerx, N. M. Velings, M. M. Mestdagh, and M. A. V. Axelos (1998). Polym. Gels Netw. 6, 393.

    Article  CAS  Google Scholar 

  23. G. A. Husseini, G. D. Myrup, W. G. Pitt, D. A. Christensen, and N. Y. Rapoport (2000). J. Control. Release 69, 43.

    Article  CAS  Google Scholar 

  24. A. Budhian, S. J. Siegel, and K. I. Winey (2007). Int. J. Pharm. 336, 367.

    Article  CAS  Google Scholar 

  25. M. L. Zweers, D. W. Grijpma, and G. H. Engbers (2003). J. Biomed. Mater. Res. B Appl. Biomater. 66, 559.

    Article  Google Scholar 

  26. T. Gorner, R. Gref, D. Michenot, et al. (1999). J. Control. Release 57, 259.

    Article  CAS  Google Scholar 

  27. A. Budhian, S. J. Siegel, and K. I. Winey (2005). J. Microencapsul. 22, 773.

    Article  CAS  Google Scholar 

  28. Y. Krishnamachari, P. Madan, and S. Lin (2007). Int. J. Pharm. 338, 238.

    Article  CAS  Google Scholar 

  29. D. Quintanar-Guerrero, H. Fessi, E. Allémann, et al. (1996). Int. J. Pharm. 143, 133.

    Article  CAS  Google Scholar 

  30. L. S. Wan and P. F. Lee (1974). J. Pharm. Sci. 63, 136.

    Article  CAS  Google Scholar 

  31. Y. Y. Yang, T. S. Chung, and N. P. Ng (2001). Biomaterials 22, 231.

    Article  CAS  Google Scholar 

  32. S. Mao, Y. Shi, L. Li, et al. (2008). Eur. J. Pharm. Biopharm. 68, 214.

    Article  CAS  Google Scholar 

  33. G. D. Rosa, R. Iommelli, M. I. La Rotonda, et al. (2000). J. Control. Release 69, 283.

    Article  CAS  Google Scholar 

  34. F. Yan, C. Zhang, Y. Zheng, et al. (2010). Nanomedicine 6, 170.

    CAS  Google Scholar 

  35. Sh Song, Zh Wang, Y. Qian, L. Zhang, and E. Luo (2012). J. Agric. Food Chem. 60, 4388.

    Article  CAS  Google Scholar 

  36. L. Mu and S. S. Feng (2003). J. Control. Release 86, 33.

    Article  CAS  Google Scholar 

  37. M. J. Santander-Ortega, A. B. Jodar-Reyes, N. Csaba, et al. (2006). J. Colloid Interface Sci. 302, 522.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran

    Fatemeh Baghbani & Fathollah Moztarzadeh

  2. Department of Metallurgy, Faculty of Mining and Metallurgical Engineering, Amirkabir University of Technology, Tehran, Iran

    Jamshid Aghazadeh Mohandesi

  3. Faculty of New Science and Technologies, Tehran University, Tehran, Iran

    Fatemeh Yazdian

  4. Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Manijhe Mokhtari-Dizaji

  5. Department of Cellulose and Paper Technology, Faculty of New Technologies and Energy Engineering, Shahid Beheshti University, Tehran, Iran

    Sepideh Hamedi

Authors
  1. Fatemeh Baghbani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fathollah Moztarzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jamshid Aghazadeh Mohandesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatemeh Yazdian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manijhe Mokhtari-Dizaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sepideh Hamedi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fatemeh Baghbani or Fathollah Moztarzadeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baghbani, F., Moztarzadeh, F., Mohandesi, J.A. et al. Optimization of Formulation and Process Variables for the Preparation of Novel Doxorubicin-Loaded Sonosensitive Nanodroplets. J Clust Sci 27, 1519–1536 (2016). https://doi.org/10.1007/s10876-016-1020-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10876-016-1020-0

Keywords

Search

Navigation