Inverse Miniemulsion Method for Synthesis of Gelatin Nanoparticles in Presence of CDI/NHS as a Non-toxic Cross-linking System

Document Type: Research Paper


1 School of Chemistry, University College of Science, University of Tehran, I.R.Iran

2 School of Chemistry, University College of Science, University of Tehran, I.R.Iran Biomaterials Research Center (BRC), University of Tehran, Tehran, I.R.Iran



In this research, gelatin nanoparticles were synthesized via inverse miniemulsion method by employing a mixture of a water soluble carbodiimide (CDI) and N-hydroxysuccinimide (NHS) as a non-toxic cross-linking system. The gelatin nanoparticles were characterized for their size and size distribution, morphology and stability and were compared with those of nanoparticles cross-linked by glutaraldehyde (GA) as the most commonly utilized cross-linking agent. The results showed the formation of more homogeneous nanoparticles with smaller size when CDI/NHS used as cross-linking agent under the same synthesis condition. Moreover, dilute solution viscosimetry experiments confirmed the stability of the nanoparticles under various physicochemical conditions. The differences in the characteristics of CDI/NHS and GA cross-linked nanoparticles were ascribed to the different nature of network formation using the two cross-linking agents. Generally, these results suggested CDI/NHS cross-linked gelatin nanoprticles as an interesting candidate for drug delivery application.


[1] H. G. Schwick and K. Heide, Bibliotheca Haematologica, 3 (1969) 111-125.

[2] A. O. Elzoghby, W. M. Samy, N. A. Elgindy, Journal of Controlled Release, 161(2012) 38-49.

[3] J. Xu, F. Gattacceca, M. Amiji, J. Mol. Pharmaceutics. 10 (2013) 2031-2044.

[4]  S. K. Nitta and K. Numata, Int. J. Mol. Sci. 14 (2013) 1629-1654. 

[5] J-H. Xu, F-P.Gao, X-F.  Liu, Q.  Zeng, Sh-Sh. Guo, Zh-Y. Tang, X-Zh. Zhao and H. Wang,J. Chem. Commun.49 (2013) 4462-4462.

[6] C. J. Coester, K. Langer, H. V. Brisen, J. Kreuter, J. Microencapsul.17 (2000) 187-193.

[7] M. Mozafari and F. Moztarzadeh, Journal of Colloid and Interface Science, 351 (2010) 442-448.

[8] C.-L. Tseng, K.-C.Yang,  K.-C.Yen,  S.Y.-H.Wu,  F.-H, Current Nanoscience, 7 (2011) 932-937.

[9] H. Wang, O. Boerman, K. Sariibrahimoglu, Y. Li, J. Jansen, S. Leeuwenburgh, Biomaterials, 33 (2012) 8695-8703.

[10] N. Kuntworbe and R. Al-Kassas, J. AAPS. Pharm. Sci. Tech. 13 (2012) 568-581.

[11]H. Wang, Q. Zou, O. Boerman, A. Nijhuis, J. Jansen, Y. Li, S. Leeuwenburgh,  Journal of Controlled Release, 166 (2013) 172-181.

[12]E. J. Lee, S. Ahmad Khan, J. K. Park, K-H. Lim, J. Bioprocess Biosyst Eng. 35 (2012) 297–307.

[13] S. Ahmad Khan, M. Schneider, J. Macromol. Biosci. 13 (2013) 455–463.

[14] R. C. Oppenheim and N. F. Stewart, Drug Dev. Ind. Pharm.5 (1979) 563-571.

[15] E. Leo, M. A. Vandelli, R. Cameroni and F. Forni, Int.J. Pharmaceut.155 (1997) 75-82.

[16] K. W. Leong, H. Q. Mao, V. L. Truong, K. Roy, S. M. Walsh and J. T. August, J.Controlled Release,53 (1998) 183-189.

[17] B. Rossler, J. Kreuter, D. Scherer,Journal of Microencapsulation, 12 (1995) 49-57.

[18] C.-P. Zhang, L .Hu, Y.-P.Luo, W. Deng, X. Gao, Y.-X. Qiu , D.-J Shen, FuheCailiaoXuebao/ActaMateriaeCompositaeSinica, 19 (2002) 59-64 .

[19] M. G. Cascone, L. Lazzeri, C. Carmignani and Z. Zhu, J. Mater. Sci.: Mater.Med.13 (2002) 523-526 .

[20] A. K. Bajpai and J. Chouby, J. Mater. Sci.: Mater. Med.17 (2006) 345-358.

[21] J. Kwon Oh, R. Drumright, D. J. Siegwart, K. Matyjaszewski, J. Prog.Polym. Sci.33 (2008) 448–477.

[22] A. Ethirajan, K. Schoeller, A. Musyanovych, U. Ziener and K. Landfester,Biomacromolecules, 9 (2008) 2383-2389.

[23]A. Ethirajan and Katharina Landfester, J.Chem. Eur. 16 (2010) 9398-9412. 

[24] N. TaheriQazvini and S. Zinatloo, J. Mater. Sci: Mater. Med.22 (2011) 63-69. 

[25] W. M. Kulicke and C. Clasen, Viscosometry of    Polymers and Polyelectrolytes.Speringer-Verlag, Berlin (2004).

[26] C. Vathier and K. Bouchemal, Pharmaceut. Res.26 (2009) 1025-1058.

[27] L. H. H. OldeDamink, P. J. Dijkstra, M. J. A. van Luyn, P. B. van Wachem, P.Nieuwenhuis, J. Feijin, J. Mater. Sci: Mater Med. 6 (1995) 460-472.

[28] E. Khor, Biomaterials,18 (1997) 95-105.

[29] A. J. Kuijpers, G. H. M. Engbers, J. Feijen, S. C. De Smedt, T. K. L. Meyvis, J.Demeester, J. Krijgsveld, S. A. J. Zaat and J. Dankert, Macromolecules,32(1999) 3325-3333.

[30] R. Timkovicz, Anal. Biochem.79 (1977) 135-143.

[31] H. Yamakawa, Macromolecules,34 (1961) 1360-1372.

[32] A. Gupta, B. Mohanty and H. B. Bohidar, Biomacromolecules,6 (2005) 1623-1627.