Enhanced therapeutic efficacy of Tamoxifen against breast cancer using extra virgin olive oil-based nanoemulsion delivery system
Source abstract
Abstract
Abstract Breast cancer remains a leading cause of cancer-related deaths worldwide, requiring innovative therapeutic approaches. This study investigated the development and characterization of an olive oil-based nanoemulsion system for enhanced tamoxifen (TMX) delivery in breast cancer treatment, pointing to the limitations of poor water solubility and bioavailability of free TMX. Extra virgin olive oil (EVOO) was initially characterized by high-performance liquid chromatography analysis, confirming its high content of oleic acid (65.45%). The oil-in-water nanoemulsion system [NE(OST) + TMX] was successfully formulated using EVOO (oil phase) with surfactants, i.e. , Tween-80 and Span-20. NE(OST) + TMX exhibited excellent physical stability with a particle size of 179.76 ± 9.6 nm, a polydispersity index of 0.184, and a zeta potential of −30.52 mV. NE(OST) + TMX demonstrated high entrapment efficiency (97.5 ± 4.25%) and a controlled release profile, achieving complete release within 24 h, to improve drug penetration and cellular uptake in cancer cells while reducing systemic toxicity. NE(OST) + TMX showed reduced in vitro hemolytic activity compared to free TMX, indicating improved biocompatibility. The cytotoxicity test showed a better antiproliferative effect against MCF-7 cells with NE(OST) + TMX (IC 50 = 49.23 μg mL −1 ) compared to free TMX (IC 50 = 90.12 μg mL −1 ), while exhibiting reduced toxicity toward normal HdFn cells. Fluorescence microscopy confirmed superior cellular uptake of NE(OST) + TMX. Flow cytometry analysis demonstrated that NE(OST) + TMX significantly increased apoptosis induction and G₀/G₁ phase cell cycle arrest compared to free TMX. NE(OST) + TMX exhibited enhanced inhibition of cell migration in wound healing assays. NE(OST) + TMX upregulated BAX and Caspase-3 and downregulated BCL-2 , confirming its molecular-level apoptotic efficacy. These results demonstrate that the olive oil nanoemulsion system significantly enhances TMX therapeutic efficacy while improving biocompatibility for breast cancer treatment.
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Research context
OpenAlex topics: Curcumin's Biomedical Applications · Nanoparticle-Based Drug Delivery · Advanced Drug Delivery Systems
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Biotechnology, College of Applied Sciences, University of Technology, Baghdad , Iraq
Department of Molecular and Medical Biotechnology, College of Biotechnology, Al-Nahrain University, Jadriya, Baghdad , Iraq
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim , 51452 , Saudi Arabia
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, Bisha , 67714 , Saudi Arabia
Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj , 11942 , Saudi Arabia
References (80)
Show source-provided references
1. Turajlic S, Sottoriva A, Graham T, Swanton C. Resolving genetic heterogeneity in cancer. Nat Rev Genet. 2019;20(7):404–16.10.1038/s41576-019-0114-6 ↗
2. Anand U, Dey A, Chandel AKS, Sanyal R, Mishra A, Pandey DK, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2023;10(4):1367–401.10.1016/j.gendis.2022.02.007 ↗
3. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clinicians. 2024;74(3):229–63.10.3322/caac.21834 ↗
4. Silva LAS, Felix FB, Araujo JMD, Souza EV, Camargo EA, Grespan R. Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice. Braz J Med Biol Res. 2017;51(1):e6799.10.1590/1414-431x20176799 ↗
5. Dehghani F, Farhadian N, Golmohammadzadeh S, Biriaee A, Ebrahimi M, Karimi M. Preparation, characterization and in-vivo evaluation of microemulsions containing tamoxifen citrate anti-cancer drug. Eur J Pharm Sci. 2017;96:479–89.10.1016/j.ejps.2016.09.033 ↗
6. Rouhimoghadam M, Safarian S, Carroll JS, Sheibani N, Bidkhori G. Tamoxifen-induced apoptosis of MCF-7 cells via GPR30/PI3K/MAPKs interactions: verification by ODE modeling and RNA sequencing. Front Physiol. 2018;9:907. 10.3389/fphys.2018.00907.10.3389/fphys.2018.00907 ↗
7. Shrivastava N, Parikh A, Dewangan RP, Biswas L, Verma AK, Mittal S, et al. Solid self-nano emulsifying nanoplatform loaded with tamoxifen and resveratrol for treatment of breast cancer. Pharmaceutics. 2022;14(7):1486. 10.3390/pharmaceutics14071486.10.3390/pharmaceutics14071486 ↗
8. Jain AK, Thanki K, Jain S. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen: part I. Formulation development, statistical optimization, and in vitro characterization. Pharm Res. 2014;31(4):923–45.10.1007/s11095-013-1213-2 ↗
9. Claro de Souza M, Marotta-Oliveira SSA, Rocha NHS, Eloy JO, Marchetti JM. Development of a method to evaluate the release profile of tamoxifen from pegylated hybrid micelles. J Liq Chromatogr Relat Technol. 2015;38(12):1223–9.10.1080/10826076.2015.1032418 ↗
10. Liu Y, Liang Y, Yuhong J, Xin P, Han JL, Du Y, et al. Advances in nanotechnology for enhancing the solubility and bioavailability of poorly soluble drugs. Drug Design Dev Ther. 2024;18:1469–95.10.2147/DDDT.S447496 ↗
11. Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer. 2023;22(1):169.10.1186/s12943-023-01865-0 ↗
12. Sani A, Pourmadadi M, Shaghaghi M, Mahdi Eshaghi M, Shahmollaghamsary S, Arshad R, et al. Revolutionizing anticancer drug delivery: Exploring the potential of tamoxifen-loaded nanoformulations. J Drug Delivery Sci Technol. 2023;86:104642.10.1016/j.jddst.2023.104642 ↗
13. Al-jubori AA, Sulaiman GM, Tawfeeq AT, Mohammed HA, Khan RA, Mohammed SAA. Layer-by-layer nanoparticles of tamoxifen and resveratrol for dual drug delivery system and potential triple-negative breast cancer treatment. Pharmaceutics. 2021;13(7):1098. 10.3390/pharmaceutics13071098.10.3390/pharmaceutics13071098 ↗
14. Abdellatif AAH, Mohammed HA, Khan RA, Singh V, Bouazzaoui A, Yusuf M, et al. Nano-scale delivery: A comprehensive review of nano-structured devices, preparative techniques, site-specificity designs, biomedical applications, commercial products, and references to safety, cellular uptake, and organ toxicity. Nanotechnol Rev. 2021;10(1):1493–559.10.1515/ntrev-2021-0096 ↗
15. Mohammed HA, Khan RA, Singh V, Yusuf M, Akhtar N, Sulaiman GM, et al. Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high-incidence cancers, and other diseases: Roles of preparation methods, lipid composition, transitional stability, and release profiles in nanocarriers’ development. Nanotechnol Rev. 2023;12(1):20220517.10.1515/ntrev-2022-0517 ↗
16. Kumar V, Garg V, Dureja H. Nanoemulsion for delivery of anticancer drugs. Cancer Adv. 2022;5:e22016.10.53388/2022522016 ↗
17. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015;5:123–7.10.1007/s13205-014-0214-0 ↗
18. Tarik Alhamdany A, Saeed AMH, Alaayedi M. Nanoemulsion and solid nanoemulsion for improving oral delivery of a breast cancer drug: Formulation, evaluation, and a comparison study. Saudi Pharm J. 2021;29(11):1278–88.10.1016/j.jsps.2021.09.016 ↗
19. Preeti, Sambhakar S, Malik R, Bhatia S, Al Harrasi A, Rani C, et al. Nanoemulsion: an emerging novel technology for improving the bioavailability of drugs. Scientifica (Cairo). 2023;2023:6640103.10.1155/2023/6640103 ↗
20. Cuyàs E, Gumuzio J, Lozano-Sánchez J, Segura-Carretero A, Verdura S, Bosch-Barrera J, et al. Mimetics of extra virgin olive oil phenols with anti-cancer stem cell activity. Aging. 2020;12(21):21057–75.10.18632/aging.202154 ↗
21. El Haouari M. Anti-cancer and cardiovascular properties of phenolic compounds present in virgin olive oil. In: Akram M, editor. Olive oil - New perspectives and applications. Rijeka: IntechOpen; 2021.10.5772/intechopen.96392 ↗
22. Guarrasi V, Mangione MR, Sanfratello V, Martorana V, Bulone D. Quantification of underivatized fatty acids from vegetable oils by HPLC with UV detection. J Chromatogr Sci. 2010;48(8):663–8.10.1093/chromsci/48.8.663 ↗
23. Tandel H, Raval K, Nayani A, Upadhay M. Preparation and evaluation of cilnidipine microemulsion. J Pharm Bioallied Sci. 2012;4(Suppl 1):S114–5.10.4103/0975-7406.94162 ↗
24. Ansaril M, Ahmed M, Anwer M, Jamil S, Alalaiwe A, Alshetaili A, et al. Formulation and characterization of fluconazole loaded olive oil nanoemulsions. Indo Am J Pharm Sci. 2017;4(4):852–60.
25. Gadhave A. Determination of hydrophilic-lipophilic balance value. Int J Sci Res. 2014;3(4):573–5.
26. Ali MS, Alam MS, Alam N, Siddiqui MR. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy. Iran J Pharm Res. 2014;13(4):1125–40.
27. Lopes CE, Langoski G, Klein T, Ferrari PC, Farago PV. A simple HPLC method for the determination of halcinonide in lipid nanoparticles: development, validation, encapsulation efficiency, and in vitro drug permeation. Braz J Pharm Sci. 2017;53(2):e15250.10.1590/s2175-97902017000215250 ↗
28. Liu M, Dasgupta A, Koczera P, Schipper S, Rommel D, Shi Y, et al. Drug loading in poly(butyl cyanoacrylate)-based polymeric microbubbles. Mol Pharm. 2020;17(8):2840–8.10.1021/acs.molpharmaceut.0c00242 ↗
29. Usmani A, Mishra A, Arshad M, Jafri A. Development and evaluation of doxorubicin self nanoemulsifying drug delivery system with Nigella Sativa oil against human hepatocellular carcinoma. Artif Cells Nanomed Biotechnol. 2019;47(1):933–44.10.1080/21691401.2019.1581791 ↗
30. Altmeyer C, Karam TK, Khalil NM, Mainardes RM. Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity. Mater Sci Eng: C. 2016;60:135–42.10.1016/j.msec.2015.11.019 ↗
31. Akram SM, Al-Saffar AZ, Hadi NA, Akram SM. Utilization of novel lectin-conjugated Au nanoparticles as Thomsen-Friedenreich onco-antigen target for in vitro cytotoxicity and apoptosis induction in leukemic cell line. Life Sci. 2022;311:121163.10.1016/j.lfs.2022.121163 ↗
32. Mahmood RI, Abbass AK, Al-Saffar AZ, Al-Obaidi JR. An in vitro cytotoxicity of a novel pH-Sensitive lectin loaded-cockle shell-derived calcium carbonate nanoparticles against MCF-7 breast tumour cell. J Drug Delivery Sci Technol. 2021;61:102230.10.1016/j.jddst.2020.102230 ↗
33. Mohammed HA, Said R, Abbas MM, Al-Najjar BO, Abd-Elmoniem E, Khan RA, et al. Phytochemical, biological, and computational investigations of Ephedra alata Decne. growing in salinity conditions of Arabian Peninsula. Sci Rep. 2024;14(1):21987.10.1038/s41598-024-69607-w ↗
34. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.10.1006/meth.2001.1262 ↗
35. Mohammed HA, Sulaiman GM, Anwar SS, Tawfeeq AT, Khan RA, Mohammed SAA, et al. Quercetin against MCF7 and CAL51 breast cancer cell lines: apoptosis, gene expression and cytotoxicity of nano-quercetin. Nanomedicine. 2021;16(22):1937–61.10.2217/nnm-2021-0070 ↗
36. Fatemizadeh M, Tafvizi F, Shamsi F, Amiri S, Farajzadeh A, Akbarzadeh I. Apoptosis induction, cell cycle arrest and anti-cancer potential of tamoxifen-curcumin loaded niosomes against MCF-7 cancer cells. Iran J Pathol. 2022;17(2):183–90.10.30699/ijp.2022.124340.2358 ↗
37. Abdallah ME, El-Readi MZ, Althubiti MA, Almaimani RA, Ismail AM, Idris S, et al. Tamoxifen and the PI3K inhibitor: LY294002 synergistically induce apoptosis and cell cycle arrest in breast cancer MCF-7 cells. Molecules. 2020;25(15):3355. 10.3390/molecules25153355.10.3390/molecules25153355 ↗
38. Alamro AA, Al-Malky MM, Ansari MGA, Amer OE, Alnaami AM, Hussain SD, et al. The effects of melatonin and vitamin D3 on the gene expression of BCl-2 and BAX in MCF-7 breast cancer cell line. J King Saud Univ - Sci. 2021;33(2):101287.10.1016/j.jksus.2020.101287 ↗
39. Al-Dulimi AG, Al-Saffar AZ, Sulaiman GM, Khalil KAA, Khashan KS, Al-Shmgani HSA, et al. Immobilization of l-asparaginase on gold nanoparticles for novel drug delivery approach as anti-cancer agent against human breast carcinoma cells. J Mater Res Technol. 2020;9(6):15394–411.10.1016/j.jmrt.2020.10.021 ↗
40. Xiang C, Xu Z, Liu J, Li T, Yang Z, Ding C. Quality, composition, and antioxidant activity of virgin olive oil from introduced varieties at Liangshan. LWT. 2017;78:226–34.10.1016/j.lwt.2016.12.029 ↗
41. Ghiasi Z, Esmaeli F, Aghajani M, Ghazi-Khansari M, Faramarzi MA, Amani A. Enhancing analgesic and anti-inflammatory effects of capsaicin when loaded into olive oil nanoemulsion: An in vivo study. Int J Pharm. 2019;559:341–7.10.1016/j.ijpharm.2019.01.043 ↗
42. Farrés-Cebrián M, Seró R, Saurina J, Núñez O. HPLC-UV polyphenolic profiles in the classification of olive oils and other vegetable oils via principal component analysis. Separations. 2016;3(4):33.10.3390/separations3040033 ↗
43. Lopez S, Bermudez B, Montserrat-de la Paz S, Pacheco YM, Ortega-Gomez A, Varela LM, et al. Chapter 53 - Oleic acid – the main component of olive oil on postprandial metabolic processes. In: Preedy VR, Watson RR, editors. Olives and olive oil in health and disease prevention (Second Edition). San Diego: Academic Press; 2021. p. 639–49.10.1016/B978-0-12-819528-4.00034-1 ↗
44. Hernández ML, Sicardo MD, Belaj A, Martínez-Rivas JM. The oleic/linoleic acid ratio in olive (Olea europaea L.) fruit mesocarp is mainly controlled by OeFAD2-2 and OeFAD2-5 genes together with the different specificity of extraplastidial acyltransferase enzymes. Front Plant Sci. 2021;12:653997. 10.3389/fpls.2021.653997.10.3389/fpls.2021.653997 ↗
45. Baccouri B, Rajhi I, Theresa S, Najjar Y, Mohamed SN, Willenberg I. The potential of wild olive leaves (Olea europaea L. subsp. oleaster) addition as a functional additive in olive oil production: the effects on bioactive and nutraceutical compounds using LC–ESI–QTOF/MS. Eur Food Res Technol. 2022;248(11):2809–23.10.1007/s00217-022-04091-y ↗
46. Wabaidur SM, AlAmmari A, Aqel A, Al-Tamrah SA, Alothman ZA, Ahmed AYBH. Determination of free fatty acids in olive oils by UPHLC–MS. J Chromatogr B. 2016;1031:109–15.10.1016/j.jchromb.2016.07.040 ↗
47. Novoselić A, Klisović D, Lukić I, Lukić M, Brkić Bubola K. The use of olive leaves in buža olive cultivar oil production: Exploring the impact on oil yield and chemical composition. Agriculture. 2021;11(10):917. 10.3390/agriculture11100917.10.3390/agriculture11100917 ↗
48. Bouymajane A, Oulad El Majdoub Y, Cacciola F, Russo M, Salafia F, Trozzi A, et al. Characterization of phenolic compounds, Vitamin E and fatty acids from monovarietal virgin olive oils of “Picholine marocaine” cultivar. Molecules. 2020;25(22):5428. 10.3390/molecules25225428.10.3390/molecules25225428 ↗
49. Jimenez-Lopez C, Carpena M, Lourenço-Lopes C, Gallardo-Gomez M, Lorenzo JM, Barba FJ, et al. Bioactive compounds and quality of extra virgin olive oil. Foods. 2020;9(8):1014. 10.3390/foods9081014.10.3390/foods9081014 ↗
50. Alajtal AI, Sherami FE, Elbagermi MA. Acid, peroxide, ester and saponification values for some vegetable oils before and after frying. AASCIT J Mater. 2018;4(2):43–7.
51. Boskou D, Camposeo S, Clodoveo M. Table olives as sources of bioactive compounds. AOCS Press; 2015. p. 217–59.10.1016/B978-1-63067-041-2.50014-8 ↗
52. Jiménez-Sánchez A, Martínez-Ortega AJ, Remón-Ruiz PJ, Piñar-Gutiérrez A, Pereira-Cunill JL, García-Luna PP. Therapeutic properties and use of extra virgin olive oil in clinical nutrition: a narrative review and literature update. Nutrients. 2022;14(7):1440. 10.3390/nu14071440.10.3390/nu14071440 ↗
53. Mangla B, Neupane YR, Singh A, Kumar P, Shafi S, Kohli K. Lipid-nanopotentiated combinatorial delivery of tamoxifen and sulforaphane: Ex vivo, in vivo and toxicity studies. Nanomedicine. 2020;15(26):2563–83.10.2217/nnm-2020-0277 ↗
54. Alyami MH, Alyami HS, Alshehri AA, Alsharif WK, Shaikh IA, Algahtani TS. Tamoxifen citrate containing topical nanoemulgel prepared by ultrasonication technique: formulation design and in vitro evaluation. Gels. 2022;8(7):456. 10.3390/gels8070456.10.3390/gels8070456 ↗
55. Bnyan R, Khan I, Ehtezazi T, Saleem I, Gordon S, O’Neill F, et al. Surfactant effects on lipid-based vesicles properties. J Pharm Sci. 2018;107(5):1237–46.10.1016/j.xphs.2018.01.005 ↗
56. Farooq A, Shafaghat H, Jae J, Jung S-C, Park Y-K. Enhanced stability of bio-oil and diesel fuel emulsion using Span 80 and Tween 60 emulsifiers. J Environ Manag. 2019;231:694–700.10.1016/j.jenvman.2018.10.098 ↗
57. Md S, Alhakamy NA, Aldawsari HM, Husain M, Kotta S, Abdullah ST, et al. Formulation design, statistical optimization, and in vitro evaluation of a naringenin nanoemulsion to enhance apoptotic activity in A549 lung cancer cells. Pharmaceuticals. 2020;13(7):152. 10.3390/ph13070152.10.3390/ph13070152 ↗
58. Mayer S, Weiss J, McClements DJ. Vitamin E-enriched nanoemulsions formed by emulsion phase inversion: Factors influencing droplet size and stability. J Colloid Interface Sci. 2013;402:122–30.10.1016/j.jcis.2013.04.016 ↗
59. Mousset E, Oturan N, van Hullebusch ED, Guibaud G, Esposito G, Oturan MA. A new micelle-based method to quantify the Tween 80® surfactant for soil remediation. Agron Sustain Dev. 2013;33(4):839–46.10.1007/s13593-013-0140-2 ↗
60. Jain AK, Thareja S. In vitro and in vivo characterization of pharmaceutical nanocarriers used for drug delivery. Artif Cells Nanomed Biotechnol. 2019;47(1):524–39.10.1080/21691401.2018.1561457 ↗
61. Yang W, Zhang X, Zhang J, Wang G, Liang H, Zhang X, et al. Determination of C═C positions of unsaturated fatty acids in foods via ambient reactive desorption ionization with water dimer radical cations. J Agric Food Chem. 2024;72(1):845–56.10.1021/acs.jafc.3c05585 ↗
62. Ejigah V, Owoseni O, Bataille-Backer P, Ogundipe OD, Fisusi FA, Adesina SK. Approaches to improve macromolecule and nanoparticle accumulation in the tumor microenvironment by the enhanced permeability and retention effect. Polymers. 2022;14(13):2601. 10.3390/polym14132601.10.3390/polym14132601 ↗
63. Rashid SA, Bashir S, Ullah H, Khan DH, Shah PA, Danish MZ, et al. Development, characterization and optimization of methotrexate-olive oil nano-emulsion for topical application. Pak J Pharm Sci. 2021;34(1):205–15.
64. Dou J, Zhang H, Liu X, Zhang M, Zhai G. Preparation and evaluation in vitro and in vivo of docetaxel loaded mixed micelles for oral administration. Colloids Surf B, Biointerfaces. 2014;114:20–7.10.1016/j.colsurfb.2013.09.010 ↗
65. Aboumanei MH, Mahmoud AF. Development of tamoxifen in situ gel nanoemulsion for ocular delivery in photoreceptor degeneration disorder: in vitro characterization, 131I-radiolabeling, and in vivo biodistribution studies. J Pharm Innov. 2023;18(2):369–80.10.1007/s12247-022-09638-w ↗
66. Layek B, Mukherjee B. Tamoxifen citrate encapsulated sustained release liposomes: preparation and evaluation of physicochemical properties. Sci Pharm. 2010;78(3):507–16.10.3797/scipharm.0911-11 ↗
67. Abdmouleh F, El Arbi M, Saad HB, Jellali K, Ketata E, Amara IB, et al. Antimicrobial, antitumor and side effects assessment of a newly synthesized tamoxifen analog. Curr Top Med Chem. 2020;20(25):2281–8.10.2174/1568026620666200819145526 ↗
68. Al-jubori AA, Tawfeeq AT, Sulaiman GM. Novel tamoxifen citrate-loaded polymeric nanoformulations for improving treatment and uses in medical applications: an in vitro and in vivo study. Iraqi J Sci. 2022;63(6):2419–33.10.24996/ijs.2022.63.6.9 ↗
69. Wu J. The enhanced permeability and retention (EPR) effect: the significance of the concept and methods to enhance its application. J Pers Med. 2021;11(8):771. 10.3390/jpm11080771.10.3390/jpm11080771 ↗
70. Öztürk-Atar K, Kaplan M, Çalış S. Development and evaluation of polymeric micelle containing tablet formulation for poorly water-soluble drug: tamoxifen citrate. Drug Dev Ind Pharm. 2020;46(10):1695–704.10.1080/03639045.2020.1820037 ↗
71. Tayeb HH, Felimban R, Almaghrabi S, Hasaballah N. Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks. Colloid Interface Sci Commun. 2021;45:100533.10.1016/j.colcom.2021.100533 ↗
72. Aldawsari HM, Negm AA. Potentiation of raloxifene cytotoxicity against MCF-7 breast cancer cell lines via transdermal delivery and loading on self-emulsifying nanoemulsions. Trop J Pharm Res. 2020;19(1):11–5.10.4314/tjpr.v19i1.2 ↗
73. Sánchez-López E, Guerra M, Dias-Ferreira J, Lopez-Machado A, Ettcheto M, Cano A, et al. Current applications of nanoemulsions in cancer therapeutics. Nanomaterials. 2019;9(6):821. 10.3390/nano9060821.10.3390/nano9060821 ↗
74. Guo L, Mao X, Li Y, Zhou Z. Polymethoxylated flavonoids (PMFs)-loaded citral nanoemulsion controls green mold in citrus by damaging the cell membrane of Penicillium digitatum. Fungal Biol. 2023;127(1–2):854–64.10.1016/j.funbio.2022.12.003 ↗
75. Vijaya Rani KR, Rajan S, Bhupathyraaj M, Priya RK, Halligudi N, Al-Ghazali MA, et al. The effect of polymers on drug release kinetics in nanoemulsion in situ gel formulation. Polymers. 2022;14(3):427. 10.3390/polym14030427.10.3390/polym14030427 ↗
76. Torić J, Karković Marković A, Jakobusic Brala C, Barbarić M. Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs. Acta Pharm (Zagreb, Croatia). 2019;69:461–82.10.2478/acph-2019-0052 ↗
77. Huang B, Luo N, Wu X, Xu Z, Wang X, Pan X. The modulatory role of low concentrations of bisphenol A on tamoxifen-induced proliferation and apoptosis in breast cancer cells. Environ Sci Pollut Res. 2019;26(3):2353–62.10.1007/s11356-018-3780-6 ↗
78. Kim HW, Park JE, Baek M, Kim H, Ji HW, Yun SH, et al. Matrix metalloproteinase-1 (MMP1) upregulation through promoter hypomethylation enhances tamoxifen resistance in breast cancer. Cancers. 2022;14(5):1232. 10.3390/cancers14051232.10.3390/cancers14051232 ↗
79. Zhang X, Wang M, Sun H, Zhu T, Wang X. Downregulation of LINC00894-002 contributes to tamoxifen resistance by enhancing the TGF-β signaling pathway. Biochem (Mosc). 2018;83(5):603–11.10.1134/S0006297918050139 ↗
80. Al-Hussaniy HA, Almajidi YQ, Oraibi AI, Alkarawi AH. Nanoemulsions as medicinal components in insoluble medicines. Pharmacia. 2023;70(3):537–47.10.3897/pharmacia.70.e107131 ↗