Advertisement

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

  • Umut Can Oz
  • Berrin Küçüktürkmen
  • Burcu Devrim
  • Ongun Mehmet SakaEmail author
  • Asuman Bozkir
Article
  • 27 Downloads

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.

Keywords

Central composite design Nanoparticle Biphosphonates PLGA 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. (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).CrossRefGoogle Scholar
  2. (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).CrossRefGoogle Scholar
  3. (3).
    F. M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, and Z. F. Wu, Biomaterials, 31, 7892 (2010).CrossRefGoogle Scholar
  4. (4).
    J. D. Bashutski and H. L. Wang, J. Endodont., 35, 321 (2009).CrossRefGoogle Scholar
  5. (5).
    W. Li, Y. Ding, S. Yu, Q. Yao, and A. R. Boccaccini, ACS Appl. Mater. Interfaces, 7, 20845 (2015).CrossRefGoogle Scholar
  6. (6).
    F. Watzinger, J. Luksch, W. Millesi, C. Schopper, J. Neugebauer, D. Moser, and R. Ewers, Br. J. Oral Maxillofac. Surg., 38, 312 (2000).CrossRefGoogle Scholar
  7. (7).
    A. Bozkir and O. M. Saka, Farmaco, 60, 840 (2005).CrossRefGoogle Scholar
  8. (8).
    C. Martins, F. Sousa, F. Araujo, and B. Sarmento, Adv. Healthc. Mater., 7, 1 (2018).CrossRefGoogle Scholar
  9. (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).CrossRefGoogle Scholar
  10. (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).CrossRefGoogle Scholar
  11. (11).
    A. Asfaram, M. Ghaedi, S. Agarwal, I. Tyagi, and V. K. Gupta, RSC Adv., 5, 18438 (2015).CrossRefGoogle Scholar
  12. (12).
    C. Celia, D. Cosco, D. Paolino, and M. Fresta, Med. Res. Rev., 31, 716 (2011).Google Scholar
  13. (13).
    J. Varshosaz, S. Ghaffari, M. R. Khoshayand, F. Atyabi, S. Azarmi, and F. Kobarfard, J. Liposome. Res., 20, 97 (2010).CrossRefGoogle Scholar
  14. (14).
    J. P. D. H. Fessi, F. Puisieux, and C. Thies, US Patent 5,118,528 (1992).Google Scholar
  15. (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).CrossRefGoogle Scholar
  16. (16).
    E. A. Taha and N. F. Youssef, Chem. Pharm. Bull., 51, 1444 (2003).CrossRefGoogle Scholar
  17. (17).
    M. E. Gindy, A. Z. Panagiotopoulos, and R. K. Prud’homme, Langmuir, 24, 83 (2008).CrossRefGoogle Scholar
  18. (18).
    S. Xie, L. Zhu, Z. Dong, X. Wang, Y. Wang, X. Li, and W. Zhou, Colloids Surf. B Biointerfaces, 83, 382 (2011).CrossRefGoogle Scholar
  19. (19).
    T. T. Asami Ono, Takuo Ogihara, Katsuhide Terada, and Kiyohiko Sugano, ADMET DMPK, 4, 335 (2016).CrossRefGoogle Scholar
  20. (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).CrossRefGoogle Scholar
  21. (21).
    S. Alimohammadi, R. Salehi, N. Amini, and S. Davaran, Bull. Korean Chem. Soc., 33, 3225 (2012).CrossRefGoogle Scholar
  22. (22).
    L. Ochiuz, C. Grigoras, M. Popa, I. Stoleriu, C. Munteanu, D. Timofte, L. Profire, and A. G. Grigoras, Molecules, 21, 858 (2016).CrossRefGoogle Scholar
  23. (23).
    S. Chen, Z. Luo, L. Wu, C. Xie, and X. Xiao, Polymer-Plastics Technology and Engineering, 57, 1873 (2018).CrossRefGoogle Scholar
  24. (24).
    S. Sultana, A. Bhatnagar, H. Rawat, D. K. Nishad, S. Talegaonkar, F. J. Ahmad, and G. Mittal, Pharm. Dev. Technol., 19, 623 (2014).CrossRefGoogle Scholar
  25. (25).
    S. Ibrahim, S. Ibrahim, and G. Akowuah, Curr. Bioact. Compd., 13, 71 (2017).CrossRefGoogle Scholar
  26. (26).
    Y. Wang, P. Li, and L. Kong, AAPS PharmSciTech, 14, 585 (2013).CrossRefGoogle Scholar

Copyright information

© The Polymer Society of Korea and Springer 2019

Authors and Affiliations

  • Umut Can Oz
    • 1
  • Berrin Küçüktürkmen
    • 1
  • Burcu Devrim
    • 1
  • Ongun Mehmet Saka
    • 1
    Email author
  • Asuman Bozkir
    • 1
  1. 1.Faculty of Pharmacy, Department of Pharmaceutical TechnologyAnkara UniversityAnkaraTurkey

Personalised recommendations