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. 2023 Jan 16;15(1):302.
doi: 10.3390/pharmaceutics15010302.

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine

Yahia Alghazwani  1 , Krishnaraju Venkatesan  1 , Kousalya Prabahar  2 , Mohamed El-Sherbiny  3   4 , Nehal Elsherbiny  5   6 , Mona Qushawy  7   8
Affiliations

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine

Yahia Alghazwani et al. Pharmaceutics. .

Abstract

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC50 value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca2+ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca2+ ions causes cells to undergo apoptosis. Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half.

Keywords: altretamine; cancer therapy; chemical precipitation method; hydroxyapatite nanoparticles; sustained delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) TEM image of the ALT-HA-NPs and (b) SEM image of ALT-HA-NPs image, red arrows indicate NPs.
Figure 2
Figure 2
Cumulative percentage of ALT released from pure ALT and the ALT-HA-NPs (n = 3, mean ± SD).
Figure 3
Figure 3
Hematolytic activity % for Milli-Q water, normal saline, ALT-HA-NPs, and HA-NPs (mean ± SD, n = 3, p <0.05).
Figure 4
Figure 4
The outcome of ALT-HA-NPs, free ALT, and HA-NPs on the JURKAT cell line (n = 3, mean ± SD) is time- and dose-dependent. *** p < 0.001 and ** p< 0.01 denotes a significant difference between free ALT and ALT-HA-NPs.
Figure 5
Figure 5
Plasma concentration–time curve after the intravenous injection of free ALT and ALT-HA-NPs in male Wistar rats (p < 0.001, mean ± SD, n = 3).
Figure 6
Figure 6
Anti-tumor activity of free ALT, ALT-HA-NPs, and blank HA-NPs (mean ± SD, n = 3). * significant compared to Control (PBS) group at p < 0.05, ** at p less than 0.01, *** at p less than 0.001.
See this image and copyright information in PMC

References

    1. Hassan M., Watari H., AbuAlmaaty A., Ohba Y., Sakuragi N. Apoptosis and Molecular Targeting Therapy in Cancer. BioMed Res. Int. 2014;2014:150845. doi: 10.1155/2014/150845. - DOI - PMC - PubMed
    1. Kim H.S., Lim J.M., Kim J.Y., Kim Y., Park S., Sohn J. Panaxydol, a Component of P Anax Ginseng, Induces Apoptosis in Cancer Cells through EGFR Activation and ER Stress and Inhibits Tumor Growth in Mouse Models. Int. J. Cancer. 2016;138:1432–1441. doi: 10.1002/ijc.29879. - DOI - PubMed
    1. Nagoor Meeran M.F., Javed H., Al Taee H., Azimullah S., Ojha S.K. Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development. Front. Pharmacol. 2017;8:380. doi: 10.3389/fphar.2017.00380. - DOI - PMC - PubMed
    1. Levingstone T.J., Herbaj S., Dunne N.J. Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration. Nanomaterials. 2019;9:1570. doi: 10.3390/nano9111570. - DOI - PMC - PubMed
    1. Kargozar S., Mollazadeh S., Kermani F., Webster T.J., Nazarnezhad S., Hamzehlou S., Baino F. Hydroxyapatite Nanoparticles for Improved Cancer Theranostics. J. Funct. Biomater. 2022;13:100. doi: 10.3390/jfb13030100. - DOI - PMC - PubMed

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