Preparation of novel quercetin-loaded solid lipid nanoparticles: Formulation and evaluation of their anticancer potential on SK-MEL-30 melanoma cell line

Year 2025, Volume: 29 Issue: 3, 996 - 1006, 04.06.2025

Uğur Karagöz , Çağlar Demirbağ , Kübra Şengönül

https://doi.org/10.12991/jrespharm.1693837

Abstract

Quercetin, a hydrophobic compound with well-documented anticancer activity, presents challenges for therapeutic application due to its water insolubility, thus representing a promising candidate for encapsulation within solid lipid nanoparticles (SLNs) to enhance its therapeutic application. In this study, SLNs were developed using an optimized formulation of Precirol ATO 5, Tween 80, Span 80, and ethanol, using the modified hot microemulsion technique. Quercetin was encapsulated within these nanoparticles, and the particle size, zeta potential, and polydispersity index (PDI) were analyzed to assess the formulation’s characteristics and stability. Final formulations were further characterized by electron microscopy. The anticancer efficacy of quercetin-loaded SLNs was evaluated in SK-MEL-30 (melanoma) and HaCaT (keratinocyte) cell lines. Additionally, an in vitro release assay was performed to monitor quercetin release dynamics. The encapsulation efficiency and release profile of quercetin were quantified using high-performance liquid chromatography (HPLC).

Keywords

Drug delivery systems , solid lipid nanoparticles , quercetin , melanoma

References

• [1] Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2-3):165-196. https://doi.org/10.1016/s0169-409x(01)00105-3.
• [2] Wissing SA, Kayser O, Müller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev. 2004;56(9):1257-1272. https://doi.org/10.1016/j.addr.2003.12.002.
• [3] German-Cortés J, Vilar-Hernández M, Rafael D, Abasolo I, Andrade F. Solid Lipid Nanoparticles: Multitasking Nano-Carriers for Cancer Treatment. Pharmaceutics. 2023;15(3):831. https://doi.org/10.3390/pharmaceutics15030831
• [4] Akanda M, Mithu MSH, Douroumis D. Solid lipid nanoparticles: An effective lipid-based technology for cancer treatment. J Drug Deliv Sci Technol [Internet]. 2023;86:104709. https://doi.org/10.1016/j.jddst.2023.104709
• [5] Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: Structure preparation and application. Adv Pharm Bull. 2015;5(3):305-313. https://doi.org/10.15171/apb.2015.043.
• [6] Duong VA, Nguyen TT, Maeng HJ. Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method. Molecules. 2020;25(20):4781. https://doi.org/10.3390/molecules25204781.
• [7] Demirel M, Yazan Y. Kati lipit nanopartiküller (SLN). Fabad J Pharm Sci. 2000;25(4):167-179.
• [8] Borges A, Freitas V, Mateus N, Fernandes I, Oliveira J. Solid Lipid Nanoparticles as Carriers of Natural Phenolic Compounds. Antioxidants (Basel). 2020;9(10):998. https://doi.org/10.3390/antiox9100998.
• [9] Harshavardhan Reddy S, Umashankar MS, Damodharan N. Formulation, characterization and applications on solid lipid nanoparticles - A review. Res J Pharm Technol. 2018;11(12):5691-5700. https://doi.org/10.5958/0974-360X.2018.01031.4.
• [10] Lotfi N, Yousefi Z, Golabi M, Khalilian P, Ghezelbash B, Montazeri M, Shams MH, Baghbadorani PZ, Eskandari N. The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update. Front Immunol. 2023;14:1077531. https://doi.org/10.3389/fimmu.2023.1077531.
• [11] Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm. 2015;93:52-79. https://doi.org/10.1016/j.ejpb.2015.03.018.
• [12] Reyes-Farias M, Carrasco-Pozo C. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int J Mol Sci. 2019;20(13):3177. https://doi.org/10.3390/ijms20133177.
• [13] Singh P, Arif Y, Bajguz A, Hayat S. The role of quercetin in plants. Plant Physiol Biochem. 2021;166:10-19. https://doi.org/10.1016/j.plaphy.2021.05.023.
• [14] Talarico L, Consumi M, Leone G, Tamasi G, Magnani A. Solid Lipid Nanoparticles Produced via a Coacervation Method as Promising Carriers for Controlled Release of Quercetin. Molecules. 2021;26(9):2694. https://doi.org/10.3390/molecules26092694.
• [15] Aghababaei F, Hadidi M. Recent Advances in Potential Health Benefits of Quercetin. Pharmaceuticals (Basel). 2023;16(7):1020. https://doi.org/10.3390/ph16071020.
• [16] Shafabakhsh R, Asemi Z. Quercetin: a natural compound for ovarian cancer treatment. J Ovarian Res. 2019;12(1):55. https://doi.org/10.1186/s13048-019-0530-4.
• [17] Nam JS, Sharma AR, Nguyen LT, Chakraborty C, Sharma G, Lee SS. Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine. Molecules. 2016;21(1):E108. https://doi.org/10.3390/molecules21010108.
• [18] Pescina S, Garrastazu G, Del Favero E, Rondelli V, Cantù L, Padula C, Santi P, Nicoli S. Microemulsions based on TPGS and isostearic acid for imiquimod formulation and skin delivery. Eur J Pharm Sci. 2018;125:223-231. https://doi.org/10.1016/j.ejps.2018.10.007.
• [19] Ashizawa K. [Nanosize Particle Analysis by Dynamic Light Scattering (DLS)]. Yakugaku Zasshi. 2019;139(2):237-248. Japanese. https://doi.org/10.1248/yakushi.18-00171-1.
• [20] Genç L, Dikmen G. Preparation and characterization of nocodazole-loaded solid lipid nanoparticles. Pharm Dev Technol. 2014;19(6):671-676. https://doi.org/10.3109/10837450.2013.819017.
• [21] Müller RH, Heinemann S. Fat emulsions for parenteral nutrition II: Characterisation and physical long-term stability of Lipofundin MCT LCT. Clin Nutr. 1993;12(5):298-309. https://doi.org/10.1016/0261-5614(93)90050-e.
• [22] Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57. https://doi.org/10.3390/pharmaceutics10020057.
• [23] Sumantran VN. Cellular chemosensitivity assays: an overview. Methods Mol Biol. 2011;731:219-236. https://doi.org/10.1007/978-1-61779-080-5_19.
• [24] Karagöz U, Kotmakçı M, Akbaba H, Çetintaş VB, Kantarcı G. Preparation and characterization of non-viral gene delivery systems with pEGFP-C1 plasmid DNA. Brazilian J Pharm Sci. 2018;54(1) :e00265. http://dx.doi.org/10.1590/s2175-97902018000117125
• [25] Kostrzewa T, Nowak I, Feliczak-Guzik A, Drzeżdżon J, Jacewicz D, Górska-Ponikowska M, Kuban-Jankowska A. Encapsulated Oxovanadium(IV) and Dioxovanadium(V) Complexes into Solid Lipid Nanoparticles Increase Cytotoxicity Against MDA-MB-231 Cell Line. Int J Nanomedicine. 2023;18:2507-2523. https://doi.org/10.2147/ijn.s403689.
• [26] Chaudhari VS, Borkar RM, Murty US, Banerjee S. Analytical method development and validation of reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous quantifications of quercetin and piperine in dual-drug loaded nanostructured lipid carriers. J Pharm Biomed Anal. 2020;186:113325. https://doi.org/10.1016/j.jpba.2020.113325.