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Biocompatible Polymeric Nanoparticles for Effective Codelivery of Tamoxifen with Ganoderic Acid A: Systematic Approach for Improved Breast Cancer Therapeutics

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Abstract

In this research work, tamoxifen (TF) and ganoderic acid A (GA-A)-loaded polymeric nanoparticles (PNP) were developed to treat MDA-MB-231 human breast cancer in the mammary breast tumour model. The developed PNP was evaluated for their in vitro and in vivo efficacy using DMBA-induced rat model. The optimized formulation was found to be with mean particle size distribution of 155.7 nm and PDI of 0.27, while TEM imaging also confirmed size in the range of 120 nm to 180 nm. Further, drug entrapment and drug loading were found to be 92.2% and 13.4%, respectively. In vitro gastrointestinal drug stability analysis showed insignificant variations (p > 0.05) in the values of particle size, PDI and drug entrapment efficiency. In vitro drug release analysis revealed a biphasic pattern with an initial drug release of 60.01% in 6 h, followed by sustained drug release up to 94.2% in 24 h. In vitro cytotoxicity studies indicated significantly reduced cell viability with IC50 reaching a minimum value after 72 h. TF with GA-A loaded PNP exhibited 11.7% tumour incidence and lowest average tumour weight (2.4 ± 1.2 g) in the DMBA-treated group of rats, thus demonstrated highest recovery and reduction in relative tumour volume. In the DMBA-induced rat breast tumor model, TF with GA-A loaded PNP showed maximal normalization of haematological parameters, mitochondrial enzymes and other parameters such as antioxidants and inflammatory cytokines. In a nutshell, the dual drug-loaded PNP outperformed over other formulations, thus signifying a superior anticancer activity in the DMBA induced breast tumor model in rats.

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References

  1. L. Yin, J. J. Duan, X. W. Bian, and S. C. Yu (2020). Triple-negative breast cancer molecular subty** and treatment progress. Breast. Cancer Res. 22 (1), 61.

    Article  PubMed  PubMed Central  Google Scholar 

  2. T. G. Lyons (2019). Targeted Therapies for Triple-Negative Breast Cancer. Curr. Treat. Options. Oncol. 20 (11), 82.

    Article  PubMed  Google Scholar 

  3. M. Koual, C. Tomkiewicz, G. Cano-Sancho, J. P. Antignac, A. S. Bats, and X. Coumoul (2020). Environmental chemicals, breast cancer progression, and drug resistance. Environ. Health 19 (1), 117.

    Article  PubMed  PubMed Central  Google Scholar 

  4. H. A. Wahba and H. A. El-Hadaad (2015). Current approaches in the treatment of triple-negative breast cancer. Cancer Biol. Med. 12 (2), 106–116.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. J. Gao, J. Liu, F. **e, Y. Lu, C. Yin, and X. Shen (2019). Co-delivery of docetaxel and salinomycin to target both breast cancer cells and stem cells by PLGA/TPGS nanoparticles. Int. J. Nanomed. 14, 9199–9216.

    Article  CAS  Google Scholar 

  6. R. Maji, N. S. Dey, B. S. Satapathy, B. Mukherjee, and S. Mondal (2014). Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy. Int. J. Nanomed. 9, 3107–3118.

    Google Scholar 

  7. A. Barbieri, V. Quagliariello, V. Del Vecchio, M. Falco, A. Luciano, N. J. Amruthraj, G. Nasti, A. Ottaiano, M. Berretta, R. V. Iaffaioli, and C. Arra (2017). Anticancer and anti-inflammatory properties of ganoderma lucidum extract effects on melanoma and triple-negative breast cancer treatment. Nutrients 9 (3), 210.

    Article  PubMed  PubMed Central  Google Scholar 

  8. R. L. McCall and R. W. Sirianni (2013). PLGA nanoparticles formed by single or double-emulsion with vitamin E-TPGS. J. Vis. Exp. 82, 51015.

    Google Scholar 

  9. C. Wollenweber, A. V. Makievski, R. Miller, and R. Daniels (2000). Adsorption of hydroxypropyl methylcellulose at the liquid/liquid interface and the effect on emulsion stability. Colloids Surf. A Physicochem. Eng. Aspects 172 (1–3), 91–101.

    Article  CAS  Google Scholar 

  10. M. Rahman, S. A. Al-Ghamdi, K. S. Alharbi, S. Beg, K. Sharma, F. Anwar, F. A. Al-Abbasi, and V. Kumar (2019). Ganoderic acid loaded nano-lipidic carriers improvise treatment of hepatocellular carcinoma. Drug Deliv. 26 (1), 782–793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. M. M. Mehanna, R. Sarieddine, J. K. Alwattar, R. Chouaib, and H. Gali-Muhtasib (2020). Anticancer activity of thymoquinone cubic phase nanoparticles against human breast cancer: formulation, cytotoxicity and subcellular localization. Int. J. Nanomed. 15, 9557–9570.

    Article  CAS  Google Scholar 

  12. H. Pelicano, W. Zhang, J. Liu, N. Hammoudi, J. Dai, R. H. Xu, and L. Pusztai (2014). Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Res. 16, 434.

    Article  PubMed  PubMed Central  Google Scholar 

  13. R. Sachan, M. Rahman, R. A. Rub, D. K. Patel, and K. Sharma (2021). Chemo preventive effects of Melastomama labathricum L. extract in mammary tumour model via inhibition of oxidative stress and inflammatory cytokines. Biomed. Pharmacother. 137, 111298.

    Article  PubMed  Google Scholar 

  14. R. J. Mailloux, R. Singh, G. Brewer, C. Auger, J. Lemire, and V. D. Appanna (2009). α-ketoglutarate dehydrogenase and glutamate dehydrogenase work in tandem to modulate the antioxidant α-ketoglutarate during oxidative stress in Pseudomonas fluorescens. J. Bacteriol. 191, 3804–3810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. S. Mansouri, A. Shahriari, H. Kalantar, and T. Moini (2017). Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumours. Biomed. Rep. 6 (4), 463–467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. G. S. Shree, K. Y. Prasad, H. S. Arpitha, U. R. Deepika, K. N. Kumar, P. Mondal, and P. Ganesan (2017). beta-carotene at physiologically attainable concentration induces apoptosis and down-regulates cell survival and antioxidant markers in human breast cancer (MCF-7) cells. Mol. Cell. Biochem. 436 (1–2), 1–12.

    Article  Google Scholar 

  17. T. Sun, J. Gao, D. Han, H. Shi, and X. Liu (2019). Fabrication and characterization of solid lipid nano-formulation of astraxanthin against DMBA-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway. Drug Deliv. 26 (1), 975–988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. S. Roy, M. Singh, A. Rawat, U. Devi, S. Gautam, R. K. Yadav, J. K. Rawat, M. K. Ansari, A. S. Saeedan, D. Kumar, and G. Kaithwas (2018). GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DMBA induced mammary gland carcinoma. Int. J. Biochem. Cell. Biol. 96, 51–62.

    Article  CAS  PubMed  Google Scholar 

  19. T. C. Chou (2010). Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70 (2), 440–446.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support provided by Taif University Researchers Supporting Project Number (TURSP-2020/33), Taif University, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Hafar Al Batin, 39524, Saudi Arabia

    Abul Barkat

  2. Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, India

    Mahfoozur Rahman

  3. Department of Pharmacology, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia

    Khalid S. Alharbi

  4. Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi Arabia

    Waleed M. Altowayan

  5. Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Aţ Ţā’if, Saudi Arabia

    Majed Alrobaian

  6. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, 11942, Saudi Arabia

    Obaid Afzal & Abdulmalik Saleh Alfawaz Altamimi

  7. Department of Clinical Nutrition, College of Applied Health Sciences in Arrass, Qassim University, P.O. Box 6666, Buraidah, 51452, Saudi Arabia

    Fahad Saad Alhodieb

  8. Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Mecca, Saudi Arabia

    Waleed H. Almalki

  9. Department of Biochemistry, Faculty of Science, Centre of Artificial Intelligence for Precision Medicines, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Hani Choudhry

  10. Department of Botany, Patliputra University, Patna, Bihar, India

    Tanuja Singh

  11. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Nanomedicine Research Lab, Jamia Hamdard, New Delhi, India

    Sarwar Beg

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  1. Abul Barkat
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  7. Abdulmalik Saleh Alfawaz Altamimi
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Correspondence to Mahfoozur Rahman.

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Barkat, A., Rahman, M., Alharbi, K.S. et al. Biocompatible Polymeric Nanoparticles for Effective Codelivery of Tamoxifen with Ganoderic Acid A: Systematic Approach for Improved Breast Cancer Therapeutics. J Clust Sci 34, 1483–1497 (2023). https://doi.org/10.1007/s10876-022-02332-4

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  • DOI: https://doi.org/10.1007/s10876-022-02332-4

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