Hydroxyapatite/nifuroxazide conjugate: Characterization, drug release and antimicrobial activity Scientific paper

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Željko Radovanović
Katarina Mihajlovski
Lidija Radovanović
Đorđe Janaćković
Rada Petrović


Synthetic hydroxyapatite (Ca10(PO4)6(OH)2, HAp) is very similar to the inorganic part of the bones and teeth of mammals. It is a well-known bio­material with good biocompatibility, osteoconductivity and bioactivity. Nifur­oxazide (C12H9N3O5, NFX) is a broad-spectrum antibacterial drug and poorly soluble in water. In order to increase the solubility of NFX, nano-sized HAp powder and raw NFX drug were mixed giving, as a result, a HAp/NFX con­ju­gate. Characterization of the raw materials and the obtained conjugate con­firmed the integration of NFX on the HAp surface. An in vitro study of drug release in simulated stomach acid and intestinal fluid showed a much faster release of NFX from HAp surface than those of the raw drug. The HAp/NFX conjugate showed excellent inhibitory effects against Gram-positive bacterium Staphylococcus aureus, Gram-negative bacterium Escherichia coli and yeast Candida albicans, proving the nano-sized HAp powder as a pro­mising drug carrier.

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Željko Radovanović, K. Mihajlovski, L. Radovanović, Đorđe Janaćković, and R. Petrović, “Hydroxyapatite/nifuroxazide conjugate: Characterization, drug release and antimicrobial activity: Scientific paper”, J. Serb. Chem. Soc., vol. 86, no. 11, pp. 1103-1112, Nov. 2021.


S. V. Dorozhkin, Hydroxyapatite and Other Calcium Orthophosphates, Nova Publisher, New York, 2017 (ISBN: 978-1-53611-897-1)

J. Klesing, S. Chernousova, M. Epple, J. Mater. Chem. 22 (2012) 199 (https://dx.doi.org/10.1039/C1JM13502C)

T. Matsumoto, M. Okazaki, M. Inoue, S. Yamaguchi, T. Kusunose, T. Toyonaga, Y. Hamada, J. Takahashi, Biomaterials 25 (2004) 3807 (https://dx.doi.org/10.1016/j.biomaterials.2003.10.081)

T. S. P. Cellet, G. M. Pereira, E. C. Muniz, R. Silva, A. F. Rubira, J. Mater. Chem., B 3 (2015) 6837 (https://dx.doi.org/10.1039/c5tb00856e)

Q. Zhao, T. Wang, J. Wang, L. Zheng, T. Jiang, G. Cheng, S. Wang, Appl. Surf. Sci. 257 (2011) 10126 (https://dx.doi.org/10.1016/j.apsusc.2011.06.161)

Y. Ryabenkova, N. Jadav, M. Conte, M. F. A. Hippler, N. Reeves-McLaren, P. D. Coates, P. Twigg, A. Paradkar, Langmuir 33 (2017) 2965 (https://dx.doi.org/10.1021/acs.langmuir.6b04510)

A. L. C. Maia, C. de Aguiar Ferreira, A. L. B. deBarros, A. T. M. e Silva, G. A. Ramal-des, A. da Silva Cunha Júnior, D. C. de Pádua Oliveira, C. Fernandes, D. C. F. Soares, J. Drug Target. 26 (2018) 592 (https://dx.doi.org/10.1080/1061186X.2017.1401078)

D. Loca, J. Locs, A. Dubnika, V. Zalite, L. Berzina-Cimdina, in Hydroxyapatite (HAp) for Biomedical Applications, М. Mucalo, Еd., 1st ed., Woodhead Publishing, Cambridge, 2015, pp.189–209 (Hardcover ISBN: 9781782420330)

Z. Yang, W. Xu, M. Ji, A. Xie, Y. Shen, M. Zhu, Eur. J. Inorg. Chem. (2017) 5621 (https://dx.doi.org/10.1002/ejic.201701081)

C. Bailly, Drug Discov. Today 24 (2019) 1930 (https://dx.doi.org/10.1016/j.drudis.2019.06.017)

L. Luo, F. Xu, H. Peng, Y. Luo, X. Tian, G. Battaglia, H. Zhang, Q. Gong, Z. Gu, K. Luo, J. Control. Release 318 (2020) 124 (https://dx.doi.org/10.1016/j.jconrel.2019.12.017)

R. T. Peterson, Cell Chem. Biol. 25 (2018) 1439 (https://dx.doi.org/10.1016/j.chembiol.2018.12.005)

N. H. Zuma, J. Aucamp, D. D. N'Da, Eur. J. Pharm. Sci. 140 (2019) 105092 (https://dx.doi.org/10.1016/j.ejps.2019.105092)

L. Chen, H. Zhu, S. Yang, B. Zhou, F. You, X. Yan, Mater. Lett. 143 (2015) 252 (https://dx.doi.org/10.1016/j.matlet.2014.12.118)

Ž. Radovanović, A. M. Kazuz, P. Vulić, L. Radovanović, Đ. Veljović, R. Petrović, Đ. Janaćković; in Proceedings of 6th International Conference on Electrical, Electronic and Computing Engineering (Ic)ETRAN (2019), Silver Lake, Serbia, Proceedings_IcETRAN_ETRAN_2019, ETRAN Society, Belgrade, Academic Mind, Belgrade, 2019, p. 676 (https://etran.rs/2019/Proceedings_IcETRAN_ETRAN_2019.pdf)

C. R. Groom, I. J. Bruno, M. P. Lightfoot, S. C. Ward, Acta Crystаllogr., B 72 (2016) 171 (https://dx.doi.org/10.1107/S2052520616003954)

M. I. Toral, M. Paine, P. Leyton, P. Richter, J. AOAC Int. 87 (2004) 1323 (https://dx.doi.org/10.1093/jaoac/87.6.1323)

N. S. Sambudi, S. Cho, K. Cho, RSC Adv. 6 (2016) 43041 (https://dx.doi.org/10.1039/C6RA03147A)

T. Bera, A. N. Vivek, S. K. Saraf, P. Ramachandrarao, Biomed. Mat. 3 (2008) 025001 (https://dx.doi.org/10.1088/1748-6041/3/2/025001)

M. Ponjavić, M. S. Nikolić, J. Nikodinović-Runić, T. Ilić-Tomić, J. Djonlagić, Int. J. Polym. Mater. 68 (2019) 308 (https://dx.doi.org/10.1080/00914037.2018.1445631).

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