Tamoxifen Citrate- loaded synthetic high-density lipoproteins: Assessment of cellular toxicity in breast cancer cells


  • Ameerah A. Radhi Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Wedad K. Ali Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Fitua Al-Saedi Department of Clinical Laboratory Sciences, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq




Tamoxifen Citrate, breast cancer, in vitro cytotoxicity


Tamoxifen Citrate (TC) is the standard endocrine therapy for estrogen receptor (ER) positive breast cancer. TC is a selective estrogen receptor modulator (SERM) whose estrogenic properties in uterus have been linked to increased side

effects like blood clots, endometrial polyps and cancer. Therefore, significant amount of research has been carried out to develop tamoxifen loaded nano-formulations with a preferential accumulation in tumor tissue rather than healthy tissues.

Synthetic high-density lipoproteins (sHDL) are novel nanocarriers with inherent active-targeting ability towards tumor cells through the ligand–receptor interaction between apolipoprotein A-I (Apo A-I) and scavenger receptor class B type I (SR-BI) overexpressed in various malignant cells. The current study was carried out to investigate whether encapsulation of TC in sHDL could improve the cytotoxic effect of TC against malignant cells. For this purpose, the cytotoxicity of TC-sHDL was evaluated in MCF-7 cell line in vitro. MTT assay demonstrated the increased cytotoxicity of TC-sHDL against cancer cells as compared with the cytotoxic effect of the free drug.


- Ahmed NS, Samec M, Liskova A, Kubatka P, Saso L. Tamoxifen and oxidative stress: an overlooked connection. Discov Oncol. 2021;12(1). DOI: https://doi.org/10.1007/s12672-021-00411-y

- British National Formulary (BNF). BMJ Group and the Royal Pharmaceutical Society of Great Britain; 2021. 997 p.

- Jordan V. Selective estrogen receptor modulation: Concept and consequences in cancer. Cancer Cell. 2004;5(1):207–13. DOI: https://doi.org/10.1016/S1535-6108(04)00059-5

- Li W, Shi X, Xu Y, Wan J, Wei S, Zhu R. Tamoxifen promotes apoptosis and inhibits invasion in estrogen-positive breast cancer MCF-7 cells. Mol Med Rep. 2017;16(1):478–84. DOI: https://doi.org/10.3892/mmr.2017.6603

- British Pharmacopoeia Commission. British Pharmacopoeia. London: The Stationery Office; 2009.

- Jose A, Ninave KM, Karnam S, Venuganti VVK. Temperature-sensitive liposomes for co-delivery of tamoxifen and imatinib for synergistic breast cancer treatment. Journal of Liposome Research. Taylor & Francis; 2019. vol 29.p153–162. DOI: https://doi.org/10.1080/08982104.2018.1502315

- Beh CY, Rasedee A, Selvarajah GT, Yazan LS, Omar AR, Foong JN, et al. Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietincoated drug delivery system. PLoS One. 2019;14(7). DOI: https://doi.org/10.1371/journal.pone.0219285

- Moin A, Ud Din Wani S, Ali Osmani R, Abu Lila AS, Khafagy E-SS, Arab HH, et al. Formulation, characterization, and cellular toxicity assessment of tamoxifen-loaded silk fibroin nanoparticles in breast cancer. Drug Deliv. 2021;28(1):1626–36. DOI: https://doi.org/10.1080/10717544.2021.1958106

- Nokhodi F, Nekoei M, Goodarzi MT. Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells. J Mater Sci Mater Med. 2022;33:24. DOI: https://doi.org/10.1007/s10856-022-06647-6

- Mooberry LK, Sabnis NA, Panchoo M, Nagarajan B, Lacko AG. Targeting the SR-B1 receptor as a gateway for cancer therapy and imaging. Front Pharmacol. 2016;7:466. DOI: https://doi.org/10.3389/fphar.2016.00466

- Mei Y, Tang L, Xiao Q, Zhang ZZ, Zhang ZZ, Zang J, et al. Reconstituted high density lipoprotein (rHDL), a versatile drug delivery nanoplatform for tumor targeted therapy. J Mater Chem B. 2021;9(3):612–33. DOI: https://doi.org/10.1039/D0TB02139C

- Scheetz LM, Yu M, Li D, Castro MG, Moon JJ, Schwendeman A. Synthetic HDL nanoparticles delivering docetaxel and cpg for chemoimmunotherapy of colon adenocarcinoma. Int J Mol Sci. 2020;21:1777. DOI: https://doi.org/10.3390/ijms21051777

- Yuan Y, Wen J, Tang J, Kan Q, Ackermann R, Olsen K, et al. Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin. Int J Nanomedicine. 2016;11:6229–38. DOI: https://doi.org/10.2147/IJN.S112835

- Gong M, Zhang Q, Zhao Q, Zheng J, Li Y, Wang S, et al. Development of synthetic high-density lipoprotein-based ApoA-I mimetic peptide-loaded docetaxel as a drug delivery nanocarrier for breast cancer chemotherapy. Drug Deliv. 2019;26(1):708–16. DOI: https://doi.org/10.1080/10717544.2019.1618420

- Wang J, Jia J, Liu J, He H, Zhang W, Li Z. Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins. Drug Deliv. 2013;20(8):356–63. DOI: https://doi.org/10.3109/10717544.2013.834418

- Sabnis N, Nair M, Israel M, McConathy WJ, Lacko AG. Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles. Int J Nanomedicine. 2012;7:975–83. DOI: https://doi.org/10.2147/IJN.S28029

- Kuai R, Subramanian C, White PT, Timmermann BN, Moon JJ, Cohen MS, et al. Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma. Int J Nanomedicine. 2017;12:6581–94. DOI: https://doi.org/10.2147/IJN.S140591

- Yin X, Lu Y, Zou M, Wang L, Zhou X, Zhang Y, et al. Synthesis and characterization of salinomycin-loaded high-density lipoprotein and its effects on cervical cancer cells and cervical cancer stem cells. Int J Nanomedicine. 2021;16:6367–82. DOI: https://doi.org/10.2147/IJN.S326089

- Ma X, Song Q, Gao X. Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery. Acta Pharm Sin B. 2018;8(1):51–63. DOI: https://doi.org/10.1016/j.apsb.2017.11.006

- Zheng C, Zhang W, Wang J, Zhai Y, Xiong F, Cai Y, et al. Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer. Acta Pharm Sin B. 2022;12(9):3726–38. DOI: https://doi.org/10.1016/j.apsb.2022.02.021

- Abed HN, Hussein AA. Ex-vivo absorption study of a novel dabigatran etexilate loaded nanostructured lipid carrier using non-everted intestinal sac model. Iraqi J Pharm Sci. 2019;28(2):37–45. DOI: https://doi.org/10.31351/vol28iss2pp37-45

- Wei B, Li Y, Ao M, Shao W, Wang K, Rong T, et al. Ganglioside GM3-Functionalized Reconstituted High-Density Lipoprotein ( GM3-rHDL ) as a Novel Nanocarrier Enhances Antiatherosclerotic Efficacy of Statins in apoE − / − C57BL / 6 Mice. Pharmaceutics. 2022;14:2534. DOI: https://doi.org/10.3390/pharmaceutics14112534

- Danışman-Kalındemirtaş F, Kariper İA, Erdemir G, Sert E, Erdem-Kuruca S. Evaluation of anticancer effects of carboplatin–gelatin nanoparticles in different sizes synthesized with newly self-assembly method by exposure to IR light. Sci Rep. 2022;12(1):10686. DOI: https://doi.org/10.1038/s41598-022-15051-7

- Bondarenko L, Terekhova V, Kahru A, Dzhardimalieva G, Kelbysheva E, Tropskaya N, et al. Sample preparation considerations for surface and crystalline properties and ecotoxicity of bare and silica-coated magnetite nanoparticles. RSC Adv. 2021;11:32227–35. DOI: https://doi.org/10.1039/D1RA05703K

- Yu X, Sun L, Tan L, Wang M, Ren X, Pi J, et al. Preparation and Characterization of PLGA–PEG–PLGA Nanoparticles Containing Salidroside and Tamoxifen for Breast Cancer Therapy. AAPS PharmSciTech. 2020;21(3):85. DOI: https://doi.org/10.1208/s12249-019-1523-8

- York P. Design of dosage forms. In: Aulton ME, Taylor KM, editors. Aultons Pharmaceutics: The Design and Manufacture of Medecines. Fourth. Edinburgh: Churchill Livingstone, Elsevier; 2013. p. 23.

- Heidari Majd M, Akbarzadeh A, Sargazi A. Evaluation of host–guest system to enhance the tamoxifen efficiency. Artif Cells, Nanomedicine Biotechnol. 2017;45(3):441–7. DOI: https://doi.org/10.3109/21691401.2016.1160916

- Linares RL, Benítez JGS, Reynoso MO, Romero CG, Sandoval-Cabrera A. Modulation of the leptin receptors expression in breast cancer cell lines exposed to leptin and tamoxifen. Sci Rep. 2019;9(1):1–9. DOI: https://doi.org/10.1038/s41598-019-55674-x

- Shaker DS, Shaker MA, Hanafy MS. Cellular uptake, cytotoxicity and in-vivo evaluation of Tamoxifen citrate loaded niosomes. Int J Pharm. 2015;493(1–2):285–94. DOI: https://doi.org/10.1016/j.ijpharm.2015.07.041

- Alawad KM, Mahdi MF, Raauf AMR. Molecular Docking study , and In vitro Evaluation of Antitumor Activity of Some New Isoxazoline and Pyrazoline Derivatives of Nabumetone against breast cancer cell line (MCF-7). Al Mustansiriyah J Pharm Sci. 2022;2(3).

- Mohammed AW, Arif IS, Jasim GA. The Cytotoxic Effect of Metformin on RD Cell Line. Al Mustansiriyah J Pharm Sci. 2019;19(1):85–94. DOI: https://doi.org/10.32947/ajps.v19i1.547

- Al-khafajy WS, Arif IS, Al-sudani BT. Synergistic effect of obeticholic acid and fasting-mimicking on proliferative, migration, and survival signaling in prostate cancer. Pharmacia. 2022;69(2):579–87. DOI: https://doi.org/10.3897/pharmacia.69.e81452

- Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, et al. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front Mol Biosci. 2020;7:193. DOI: https://doi.org/10.3389/fmolb.2020.00193

- Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy : Challenges , opportunities , and clinical applications. J Control Release. 2015;200:138–57. DOI: https://doi.org/10.1016/j.jconrel.2014.12.030

- Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):1–17. DOI: https://doi.org/10.3390/pharmaceutics10020057

- Ramírez-García G, Trapiella-Alfonso L, D’Orlyé F, D’Orlyé A. Electrophoretic methods for characterizing nanoparticles and evaluating their bio-interactions for their further use as diagnostic, imaging, or therapeutic tools. In: Colin F. Poole, editor. Handbooks in Separation Science, Capillary Electromigration Separation Methods. Elsevier; 2018. p: 397–421. DOI: https://doi.org/10.1016/B978-0-12-809375-7.00019-8

- Fazel M, Daeihamed M, Osouli M, Almasi A, Haeri A, Dadashzadeh S. Preparation, in-vitro characterization and pharmacokinetic evaluation of brij decorated doxorubicin liposomes as a potential nanocarrier for cancer therapy. Iran J Pharm Res. 2018;17(Special Issue 2):33–43.




How to Cite

Ameerah A. Radhi, Wedad K. Ali, & Fitua Al-Saedi. (2023). Tamoxifen Citrate- loaded synthetic high-density lipoproteins: Assessment of cellular toxicity in breast cancer cells. Al Mustansiriyah Journal of Pharmaceutical Sciences, 23(1), 58–67. https://doi.org/10.32947/ajps.v23i1.987