Skip to main content
Log in

Development and Optimization of Alendronate Sodium Loaded PLGA Nanoparticles by Central Composite Design

  • Article
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

Alendronate sodium (AS) which supresses the activity of osteoclastic cells and leads to the inhibition of bone resorption, is one of the most clinically preferred drug for the treatment of osteoporosis. The purpose of this research is to develop an optimization method for AS loaded poly(lactide-co-glycolide) (PLGA) nanoparticle formulation which is prepared by nanoprecipitation method and is intended for local application to provide enhanced guided bone regeneration. Nanoparticle formulation parameters including AS content, polymer/surfactant ratio and organic to aqueous phase ratio were optimized to evaluate their effects on particle size, polydispersity index (PDI), zeta potential and entrapment efficiency by using central composite experimental design (CCD). Morphology of nanoparticles was visualized with transmission electron microscopy (TEM) and interaction between nanoparticle components was analyzed by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The developed quadratic model showed high correlation (R2>0.89) between predicted response and evaluated parameters. Spherical nanoparticles with mean particle size of <84 nm and encapsulation efficiency with >34.68% were produced with the optimized nanoparticle preparation method. The optimization of AS encapsulating PLGA nanoparticles by utilizing CCD method, allowed us to prepare the nanoparticle formulation with optimum properties with less experiments. Consequently, this optimized model can be applied to predict the characteristics of nanoparticles prepared with nanoprecipitation method by using PLGA polymer.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. H. G. Bone, D. Hosking, J. Devogelaer, J. R. Tucci, R. D. Emkey, R. P. Tonino, J. A. Rodriguez Portales, R. W. Downs, J. Gupta, A. C. Santora, U. A. Liberman, and A. P. I. Osteoporosis, New Engl. J. Med., 350, 1189 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. S. J. Hwang, J. S. Lee, T. K. Ryu, R. H. Kang, K. Y. Jeong, D. R. Jun, J. M. Koh, S. E. Kim, and S. W. Choi, Macromol. Res., 24, 623 (2016).

    Article  CAS  Google Scholar 

  3. F. M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, and Z. F. Wu, Biomaterials, 31, 7892 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. J. D. Bashutski and H. L. Wang, J. Endodont., 35, 321 (2009).

    Article  Google Scholar 

  5. W. Li, Y. Ding, S. Yu, Q. Yao, and A. R. Boccaccini, ACS Appl. Mater. Interfaces, 7, 20845 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. F. Watzinger, J. Luksch, W. Millesi, C. Schopper, J. Neugebauer, D. Moser, and R. Ewers, Br. J. Oral Maxillofac. Surg., 38, 312 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. A. Bozkir and O. M. Saka, Farmaco, 60, 840 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. C. Martins, F. Sousa, F. Araujo, and B. Sarmento, Adv. Healthc. Mater., 7, 1 (2018).

    Article  Google Scholar 

  9. C. G. Park, M. Park, B. H. Kim, S. H. Lee, J. Y. Park, H. H. Park, K. Lee, H. K. Seok, and Y. B. Choy, Macromol. Res., 25, 756 (2017).

    Article  CAS  Google Scholar 

  10. J. Hao, F. Wang, X. Wang, D. Zhang, Y. Bi, Y. Gao, X. Zhao, and Q. Zhang, Eur. J. Pharm. Sci., 47, 497 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. A. Asfaram, M. Ghaedi, S. Agarwal, I. Tyagi, and V. K. Gupta, RSC Adv., 5, 18438 (2015).

    Article  CAS  Google Scholar 

  12. C. Celia, D. Cosco, D. Paolino, and M. Fresta, Med. Res. Rev., 31, 716 (2011).

    CAS  PubMed  Google Scholar 

  13. J. Varshosaz, S. Ghaffari, M. R. Khoshayand, F. Atyabi, S. Azarmi, and F. Kobarfard, J. Liposome. Res., 20, 97 (2010).

    Article  CAS  PubMed  Google Scholar 

  14. J. P. D. H. Fessi, F. Puisieux, and C. Thies, US Patent 5,118,528 (1992).

    Google Scholar 

  15. Y. J. Kim, K. P. Lee, D. Y. Lee, Y. T. Kim, D. Koh, Y. Lim, and M. S. Yoon, Macromol. Res., 27, 48 (2019).

    Article  CAS  Google Scholar 

  16. E. A. Taha and N. F. Youssef, Chem. Pharm. Bull., 51, 1444 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. M. E. Gindy, A. Z. Panagiotopoulos, and R. K. Prud’homme, Langmuir, 24, 83 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. S. Xie, L. Zhu, Z. Dong, X. Wang, Y. Wang, X. Li, and W. Zhou, Colloids Surf. B Biointerfaces, 83, 382 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. T. T. Asami Ono, Takuo Ogihara, Katsuhide Terada, and Kiyohiko Sugano, ADMET DMPK, 4, 335 (2016).

    Article  Google Scholar 

  20. L. Wang, Y. W. Hao, H. X. Li, Y. L. Zhao, D. H. Meng, D. Li, J. J. Shi, H. L. Zhang, Z. Z. Zhang, and Y. Zhang, J. Drug Target., 23, 832 (2015).

    Article  CAS  PubMed  Google Scholar 

  21. S. Alimohammadi, R. Salehi, N. Amini, and S. Davaran, Bull. Korean Chem. Soc., 33, 3225 (2012).

    Article  CAS  Google Scholar 

  22. L. Ochiuz, C. Grigoras, M. Popa, I. Stoleriu, C. Munteanu, D. Timofte, L. Profire, and A. G. Grigoras, Molecules, 21, 858 (2016).

    Article  PubMed Central  Google Scholar 

  23. S. Chen, Z. Luo, L. Wu, C. Xie, and X. Xiao, Polymer-Plastics Technology and Engineering, 57, 1873 (2018).

    Article  CAS  Google Scholar 

  24. S. Sultana, A. Bhatnagar, H. Rawat, D. K. Nishad, S. Talegaonkar, F. J. Ahmad, and G. Mittal, Pharm. Dev. Technol., 19, 623 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. S. Ibrahim, S. Ibrahim, and G. Akowuah, Curr. Bioact. Compd., 13, 71 (2017).

    Article  CAS  Google Scholar 

  26. Y. Wang, P. Li, and L. Kong, AAPS PharmSciTech, 14, 585 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ongun Mehmet Saka.

Additional information

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgment: This research is funded by Turkish Scientific and Technological Research Council (TÜBİTAK grant number 112S533).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oz, U.C., Küçüktürkmen, B., Devrim, B. et al. Development and Optimization of Alendronate Sodium Loaded PLGA Nanoparticles by Central Composite Design. Macromol. Res. 27, 857–866 (2019). https://doi.org/10.1007/s13233-019-7119-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-019-7119-z

Keywords

Navigation