Abstract
In this research, controlled delivery of hollow nanoparticles from zein, the corn storage protein, to different organs of mice was achieved via crosslinking using citric acid, a non-toxic polycarboxylic acid derived from starch. Besides, crosslinking significantly enhanced water stability of nanoparticles while preserving their drug loading efficiency. Protein nanoparticles have been widely investigated as vehicles for delivery of therapeutics. However, protein nanoparticles were not stable in physiological conditions, easily cleared by mononuclear phagocyte system (MPS), and thus mainly accumulated and degraded in spleen and liver, the major MPS organs. Effective delivery to major non-MPS organs, such as kidney, was usually difficult to achieve, as well as long resident time of nanoparticles. In this research, hollow zein nanoparticles were chemically crosslinked with citric acid. Controlled delivery and prolonged accumulation of the nanoparticles in kidney, one major non-MPS organ, were achieved. The nanoparticles showed improved stability in aqueous environment at pH 7.4 without affecting the adsorption of 5-FU, a common anticancer drug. In summary, citric acid crosslinked hollow zein nanoparticles could be potential vehicles for controllable delivery of anticancer therapeutics.
Similar content being viewed by others
References
C.P. Barnes, I.C. Pemble, D.D. Brand, D.G. Simpson, G.L. Bowlin, Tissue Eng. 13, 1593 (2007)
L. Brannon-Peppas, J.O. Blanchette, Adv. Drug Deliv. Rev. 64, 206 (2012)
S. Cai, H. Xu, Q. Jiang, Y. Yang, Langmuir 29, 2311 (2013)
A.-Z. Chen, Y. Li, F.-T. Chau, T.-Y. Lau, J.-Y. Hu, Z. Zhao, D.K.-W. Mok, Acta Biomater. 5, 2913 (2009)
H.S. Choi, W. Liu, P. Misra, E. Tanaka, J.P. Zimmer, B.I. Ipe, M.G. Bawendi, J.V. Frangioni, Renal clearance of quantum dots. Nat. Biotechnol. 25, 1165 (2007)
R. Cortesi, C. Nastruzzi, S. Davis, Biomaterials 19, 1641 (1998)
R.B. Diasio, T. Beavers, J. Carpenter, J. Clin. Invest. 81, 47 (1988)
J.A. Eldridge, G.R. Willmott, W. Anderson, R. Vogel, J. Colloid Interface Sci. 429, 45 (2014)
A.O. Elzoghby, W.S. Abo El-Fotoh, N.A. Elgindy, J. Control. Release 153, 206 (2011)
A.O. Elzoghby, W.M. Samy, N.A. Elgindy, J. Control. Release 157, 168 (2012a)
A.O. Elzoghby, W.M. Samy, N.A. Elgindy, J. Control. Release 161, 38 (2012b)
E. Gendler, S. Gendler, M. Nimni, J. Biomed. Mater. Res. 18, 727 (1984)
S. Goenka, V. Sant, S. Sant, J. Control. Release 173, 75 (2014)
H. Hatakeyama, H. Akita, E. Ito, Y. Hayashi, M. Oishi, Y. Nagasaki, R. Danev, K. Nagayama, N. Kaji, H. Kikuchi, Biomaterials 32, 4306 (2011)
W. Hennink, C. Van Nostrum, Adv. Drug Deliv. Rev. 64, 223 (2012)
C.C. Hsieh, S.B. Huang, P.C. Wu, D.B. Shieh, G.B. Lee, Biomed. Microdevices 11, 903 (2009)
S.M. Janib, A.S. Moses, J.A. MacKay, Adv. Drug Deliv. Rev. 62, 1052 (2010)
Q. Jiang, N. Reddy, Y. Yang, Acta Biomater. 6, 4042 (2010)
J. Keramat, A. LeBail, C. Prost, N. Soltanizadeh, Food Bioprocess Technol. 4, 340 (2011)
J.A. Kim, H.J. Lee, H.J. Kang, T.H. Park, Biomed. Microdevices 11, 287 (2009)
L. Lai, H. Guo, Int. J. Pharm. 404, 317 (2011)
T. Lin, C. Lu, L. Zhu, T. Lu, AAPS PharmSciTech 12, 172 (2011)
Y. Luo, B. Zhang, M. Whent, L.L. Yu, Q. Wang, Colloids Surf. B 85, 145 (2011)
Y. Luo, Z. Teng, T.T. Wang, Q. Wang, J. Agric. Food Chem. 61, 7621 (2013)
H. Maeda, H. Nakamura, J. Fang, Adv. Drug Deliv. Rev. 65, 71 (2013)
A. MaHam, Z. Tang, H. Wu, J. Wang, Y. Lin, Small 5, 1706 (2009)
J.H. Park, G. Saravanakumar, K. Kim, I.C. Kwon, Adv. Drug Deliv. Rev. 62, 28 (2010)
N. Reddy, Y. Yang, Trends Biotechnol. 29, 490 (2011)
N. Reddy, Y. Li, Y. Yang, Biotechnol. Progr. 25, 139 (2009)
N. Reddy, H. Xu, Y. Yang, Biotechnol. Bioeng. 108, 1726 (2011)
F. Tanaka, T. Fukuse, H. Wada, M. Fukushima, Curr. Pharm. Biotechnol. 1, 137 (2000)
Z. Teng, Y. Li, Y. Luo, B. Zhang, Q. Wang, Biomacromolecules 14, 2848 (2013)
G.D. Venkatasubbu, S. Ramasamy, G.P. Reddy, J. Kumar, Biomed. Microdevices 15, 711 (2013)
C. Wong, T. Stylianopoulos, J. Cui, J. Martin, V.P. Chauhan, W. Jiang, Z. Popović, R.K. Jain, M.G. Bawendi, D. Fukumura, Proc. Natl. Acad. Sci. 108, 2426 (2011)
H. Xu, Q. Jiang, N. Reddy, Y. Yang, J. Mater. Chem. 21, 18227 (2011)
H. Xu, Y. Zhang, Q. Jiang, N. Reddy, Y. Yang, J. Environ. Manag. 125, 3 (2013)
Y. Yang, N. Reddy, Int. J. Biol. Macromol. 51, 37 (2012)
Y. Yang, L. Wang, S. Li, J. Appl. Polym. Sci. 59, 433 (1996)
Acknowledgments
This research was financially supported by Nebraska Corn Board, the Key Scientific and Technological Projects of Science and Technology Commission of Shanghai Municipality (12JC1400300), USDA (Hatch Act, Multistate Research Project S-1054 (NEB 37–037)), and the Agricultural Research Division at the University of Nebraska-Lincoln. The authors also thank Dr. Han Chen for his help in TEM.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xu, H., Shen, L., Xu, L. et al. Controlled delivery of hollow corn protein nanoparticles via non-toxic crosslinking: in vivo and drug loading study. Biomed Microdevices 17, 8 (2015). https://doi.org/10.1007/s10544-014-9926-5
Published:
DOI: https://doi.org/10.1007/s10544-014-9926-5