PREPARATION AND EVALUATION OF A CHITOSAN HYDROGEL-BASED SLOW-RELEASE SYSTEM LOADED WITH DOCETAXEL AND EUPHORBIA MICROSCIADIA FOR BREAST CANCER THERAPY IN A MURINE MODEL

Authors

  • MAJID ASADI SAMANI Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • DHIYA ALTEMEMY Department of Pharmaceutics, College of Pharmacy, Al-Zahraa University for Women, Karbala, Iraq
  • ARMIN AMINI Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
  • MOHSEN SAFAEI Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
  • ELHAM BIJAD Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • AKRAM ALIZADEH Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
  • PEGAH KHOSRAVIAN Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

DOI:

https://doi.org/10.22159/ijap.2026v18i2.55517

Keywords:

Cancer, Euphorbia, Solubility, Controlled release, Animal model

Abstract

Objective: To develop and evaluate a thermosensitive chitosan hydrogel co-loaded with docetaxel and a standardized E. microsciadia extract for breast cancer treatment in a murine 4T1 model.

Methods: The aerial parts of E. microsciadia were collected and identified. A chitosan hydrogel was prepared and loaded with docetaxel and Euphorbia extract. The morphological characteristics of the hydrogel were evaluated using scanning electron microscopy (SEM). Subsequently, the in vitro release profiles of docetaxel and Euphorbia extract from the hydrogel were determined. The antitumor efficacy of the prepared hydrogels was assessed in tumor-bearing mice by monitoring tumor size reduction, followed by histopathological examination of excised tumor tissues.

Results: SEM confirmed hydrogel crosslinking with 5–10 µm pore sizes versus 10–20 µm in controls. Initial release of 60% of both agents occurred within 10 h, reaching 80% by 72 h. Docetaxel and E. microsciadia significantly reduced tumor volumes compared to control (p<0.001). The combination treatment showed no significant difference from docetaxel alone (p>0.05), suggesting no synergistic effect. Histology revealed that combination therapy (docetaxel+E. microsciadia) exhibited superior tumor suppression, with significant cell degeneration and necrosis compared to other treatments.

Conclusion: The co-loaded thermosensitive chitosan hydrogel provides controlled release and effective in vivo antitumor activity. Lack of synergy warrants further optimization to enhance clinical relevance versus current docetaxel systems.

References

1. Khan MM, Yalamarty SS, Rajmalani BA, Filipczak N, Torchilin VP. Recent strategies to overcome breast cancer resistance. Crit Rev Oncol Hematol. 2024;197:104351. doi: 10.1016/j.critrevonc.2024.104351, PMID 38615873.

2. Abouzeid HA, Kassem L, Liu X, Abuelhana A. Paclitaxel resistance in breast cancer: current challenges and recent advanced therapeutic strategies. Cancer Treat Res Commun. 2025;43:100918. doi: 10.1016/j.ctarc.2025.100918, PMID 40215760.

3. Alalawy AI. Key genes and molecular mechanisms related to paclitaxel resistance. Cancer Cell Int. 2024;24(1):244. doi: 10.1186/s12935-024-03415-0, PMID 39003454.

4. Bayat Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022-43. doi: 10.18632/oncotarget.16723, PMID 28410237.

5. Lee JH, Nan A. Combination drug delivery approaches in metastatic breast cancer. J Drug Deliv. 2012;2012(1):915375. doi: 10.1155/2012/915375, PMID 22619725.

6. Aleksandrov M, Maksimova V, Koleva Gudeva L. Review of the anticancer and cytotoxic activity of some species from genus Euphorbia. Agric Conspect Sci. 2019 Mar 25;84(1):1-5.

7. Asadi Samani M, Rafieian Kopaei M, Lorigooini Z, Shirzad H. A screening to determine total phenol and flavonoid content of some Iran’s medicinal plants grown in Chaharmahal va Bakhtyari province. Indian J Nat Prod Resour. 2019;9(4):296-302. doi: 10.56042/ijnpr.v9i4.22122.

8. Asadi Samani M, Rafieian Kopaei M, Lorigooini Z, Shirzad H. A screening of growth inhibitory activity of Iranian medicinal plants on prostate cancer cell lines. Biomedicine. 2018;8(2):8. doi: 10.1051/bmdcn/2018080208, PMID 29806586.

9. Asadi Samani M, Rafieian Kopaei M, Lorigooini Z, Shirzad H. A screening of anti-breast cancer effects and antioxidant activity of twenty medicinal plants gathered from Chaharmahal va Bakhtyari province Iran. J Pharm Pharmacogn Res. 2019;7(1):213-22. doi: 10.56499/jppres19.611_7.3.213.

10. Phalak SD, Bodke VI, Yadav RE, Pandav SA, Ranaware MA. A systematic review on nano drug delivery system: solid lipid nanoparticles (SLN). Int J Curr Pharm Sci. 2024;16(1):10-20. doi: 10.22159/ijcpr.2024v16i1.4020.

11. Khoee S, Kardani M. Hydrogels as controlled drug delivery carriers. Polymerization. 2013;2(4):16-27. doi: 10.22063/basparesh.2013.955.

12. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 2001;53(3):321-39. doi: 10.1016/s0169-409x(01)00203-4, PMID 11744175.

13. Popat A, Liu J, Lu GQ, Qiao SZ. A pH-responsive drug delivery system based on chitosan-coated mesoporous silica nanoparticles. J Mater Chem. 2012;22(22):11173. doi: 10.1039/c2jm30501a.

14. Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives as intestinal absorption enhancers. Adv Drug Deliv Rev. 2001;50(Suppl 1):S91-101. doi: 10.1016/S0169-409X(01)00180-6, PMID 11576697.

15. Kalnina Z, Lieknina I, Kotelovica S, Petrovska R, Zvinys G, Petrosiute A. Development of 4T1 breast cancer mouse model system for preclinical carbonic anhydrase IX studies. FEBS Open Bio. 2025 May 15;15(8):1285-302. doi: 10.1002/2211-5463.70052, PMID 40371725.

16. Andrgie AT, Tsai HC. Hydrogels as local depots for on-demand therapeutic delivery: potential therapeutic approaches for tumor metastasis. Mater Adv. 2024;5(9):3629-43. doi: 10.1039/d4ma00122b.

17. Javdani M, Barzegar A, Khosravian P, Hashemnia M. Evaluation of inflammatory response due to use of controlled release drug delivery system of chitosan hydrogel loaded with buprenorphine and ketorolac in rat with experimental proximal tibial epiphysis defect. J Invest Surg. 2022;35(5):996-1011. doi: 10.1080/08941939.2021.1989728, PMID 34666588.

18. Riet K, Adegoke A, Mashele S, Sekhoacha M. Effective use of Euphorbia milii DCM root extract encapsulated by thermosensitive immunoliposomes for targeted drug delivery in prostate cancer cells. Curr Issues Mol Biol. 2024;46(11):12037-60. doi: 10.3390/cimb46110714, PMID 39590308.

19. Abo-Dola MA, Lutfi MF. Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats. Int J Health Sci (Qassim). 2016;10(1):69-75. doi: 10.12816/0033255, PMCID PMC4791159, PMID 27004059.

20. Gras J. Ingenol mebutate: a new option for actinic keratosis treatment. Drugs Today (Barc). 2013;49(1):15-22. doi: 10.1358/dot.2013.49.1.1910723, PMID 23362492.

Published

07-03-2026

How to Cite

SAMANI, M. A., ALTEMEMY, D., AMINI, A., SAFAEI, M., BIJAD, E., ALIZADEH, A., & KHOSRAVIAN, P. (2026). PREPARATION AND EVALUATION OF A CHITOSAN HYDROGEL-BASED SLOW-RELEASE SYSTEM LOADED WITH DOCETAXEL AND EUPHORBIA MICROSCIADIA FOR BREAST CANCER THERAPY IN A MURINE MODEL. International Journal of Applied Pharmaceutics, 18(2), 43–48. https://doi.org/10.22159/ijap.2026v18i2.55517

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