ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 19, No. 2, 2026
P. 5-15, Bibliography 55, Engl.
UDC: 606.61:615.014:615.456.3
doi: https://doi.org/10.15407/biotech19.02.005
EFFECTIVENESS OF LIPOSOMAL DRUG DELIVERY SYSTEMS FOR CREATING THERAPEUTIC FORMS OF QUERCETIN
D. М. Pylypenko1, G. S. Grigoryeva 2, Yu. М. Krasnopolsky 3
1 State Biotechnological University, Ukraine
2 State Institution “Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine”
3 National Technical University "Kharkiv Polytechnic Institute", Ukraine
Quercetin is a well-known natural antioxidant with a wide spectrum of pharmacological activities, including in oncology, cardiology, ophthalmology, and other areas. Quercetin's lipophilic nature limits its clinical use and necessitates the development of effective delivery systems. Liposomal forms of quercetin are being actively studied and improved.
Aim. The article analyzes modern research on liposomal formulations of quercetin as a promising drug-delivery strategy.
Materials and methods. Analysis of modern national and foreign research on the creation of liposomal forms of quercetin and the evaluation of the efficacy of this drug delivery system in the treatment of oncological, cardiological, viral, and other diseases accompanied by oxidative stress. To search for sources of information for the study, open-access electronic resources of scientific periodicals were used.
Results. The development of liposomal quercetin formulations enabled increased bioavailability and expanded administration options, including injection. The use of liposomal quercetin in complex cancer therapy increased tumor growth inhibition while reducing side effects in healthy tissues. To improve the efficacy of quercetin delivery to tissues, it was proposed to modify liposome surfaces with hyaluronic acid, mycophenolic acid, polyethylene glycol, and magnetic particles. The possibility of using other carriers for quercetin delivery was demonstrated, including solid lipid nanoparticles, gold nanoparticles, and polymers.
Conclusions. Quercetin nanopreparations demonstrate high pharmacological efficacy and a significant increase in quercetin bioavailability, and their safety, biodegradability, and reduced toxicity are also important.
Keywords: quercetin, antioxidant, anticancer therapy, dosage form, drug delivery system, nanoparticle, liposome, bioavailability.
D. М. Pylypenko, https://orcid.org/0000-0002-4727-0476
G. Grigoryeva, https://orcid.org/0009-0009-5079-4295
Yu. М. Krasnopolsky, https://orcid.org/0000-0003-3469-5827
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2026
{accordion title="References" open="false"}
1. Huk, I., Brovkovych, V., Nanobash Vili, J., Weigel, G., Neumayer, C., Partyka, L., …, Malinski, T. (1998). Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. The British journal of surgery, 85(8), 1080–1085. https://doi.org/10.1046/j.1365-2168.1998.00787.x
2. Kovalev, V. B., Kovgan, V. V., Tolchina, E. Yu. (1999). Mechanisms of therapeutic actions of he bioflavonoid quercetin (literature review).Ukrainskyi medychnyi almanakh, 2(4), 176–184. (In Ukrainian).
3. Stefanov, O. V., Tumanov, V. A., Garinova, N. O. (2002). Pouring Lipina onto aphids quercetin on lipid oxidation peroxide in the blood and organs of the vaginal squints during aximum physical attention. Liki, 3–4, 70–72. (In Ukrainian)
4. Lotfi, N., Yousefi, Z., Golabi, M., Khalilian, P., Ghezelbash, B., Montazeri, M., …, Eskandari, N.
(2023). The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update. Frontiers in immunology,
14, 1077531. https://doi.org/10.3389/fimmu.2023.1077531
5. Safi, A., Heidarian, E., Ahmadi, R. (2021). Quercetin Synergistically Enhances the Anticancer Efficacy of Docetaxel through Induction of Apoptosis and Modulation of PI3K/AKT, APK/ERK, and JAK/STAT3 Signaling Pathways in MDA-MB-231 Breast Cancer Cell Line. International journal of molecular and cellular medicine, 10(1), 11–22. https://doi.org/10.22088/IJMCM. BUMS.10.1.11
6. Pylypenko, D. M., Gorbach, T. V., Katsai, O. G., Grigoryeva, A. S., Krasnopolsky, Y. M. (2019). A study of oxidative stress markers when using the liposomal antioxidant complex. Pharmakeftiki, 31(1), 40–47.
7. Pylypenko, D., Gorbach, T., Krasnopolsky, Yu. (2020). Study of antioxidant activity of liposomal forms of quercetin and curcumin ischemic heart disease. BioTechnologia, 101(4), 273–282. https://doi.org/10.5114/bta.2020.100420
8. Krasnopolsky, Y. M., Dudnichenko, А. S. (2017).Experimental study of liposomal docetaxel analysis of docetaxel incorporation and stability. Experimental oncology, 39(2), 121–123.
9. Prieto-Vila, M., Shimomura, I., Kogure, A., Usuba, W., Takahashi, R. U., Ochiya, T., mamoto, Y. (2020). Quercetin Inhibits Lef1 and Resensitizes Docetaxel-Resistant Breast Cancer Cells. Molecules (Basel, Switzerland), 25(11), 2576. https://doi.org/10.3390/molecules25112576
10. Lu, X., Yang, F., Chen, D., Zhao, Q., Chen, D., Ping, H., Xing, N. (2020). Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. International journal of biological sciences, 16(7), 1121–1134. https://doi.org/10.7150/ijbs.41686
11. Hussain, Y., Mirzaei, S., Ashrafizadeh, M., Zarrabi, A., Hushmandi, K., Khan, H., Daglia, M. (2021). Quercetin and Its Nano-Scale Delivery Systems in Prostate Cancer Therapy: Paving the Way for Cancer Elimination and Reversing Chemoresistance. Cancers, 13(7), 1602. https://doi.org/10.3390/cancers13071602
12. Altintas, R., Ciftci, O., Aydin, M., Akpolat, N., Oguz, F., Beytur, A. (2015). Quercetin prevents docetaxel-induced testicular damage in rats. Andrologia, 47(3), 248–256. https://doi.org/10.1111/and.12253
13. Sharma, S., Cwiklinski, K., Mahajan, S. D., Schwartz, S. A., Aalinkeel, R. (2023). Combination Modality Using Quercetin to Enhance the Efficacy of Docetaxel in Prostate Cancer Cells. Cancers, 15(3), 902. https://doi.org/10.3390/cancers15030902
14. Ujjan, I. D., Khan, S., Nigar, R., Ahmed, H., Ahmad, S., Khan, A. (2023). The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial. Frontiers in nutrition, 9, 1023997. https://doi.org/10.3389/fnut.2022.1023997
15. Jain, A., Madu, C. O., Lu, Y. (2021). Phytochemicals in Chemoprevention: A Cost-Effective Complementary Approach. Journal of Cancer, 12(12), 3686–3700. https://doi.org/10.7150/jca.57776
16. Alexopoulou, E., Georgopoulos, A., Kagkadis, K. A., Demetzos, C. (2006). Preparation and characterization of lyophilized liposomes with incorporated quercetin. Journal of liposome research, 16(1), 17–25. https://doi.org/10.1080/08982100500528594
17. de Albuquerque, P. B. S., de Souza, M. P., Bourbon, A. I., Cerqueira, M. A., Pastrana, L., Jauregi, P., …, das Graças Carneiroda-Cunha, M. (2023). Production and roperties of Quercetin-Loaded Liposomes and Their Influence on the Properties of Galactomannan-Based Films. Applied Nano, 4(2), 159–177. https://doi.org/10.3390/applnano4020009
18. Patent of Ukraine No. 76393. Method for extracting liposomal extract, which take quercetin. 2007. Stefanov, O. V., Grigor'eva, G. WITH., Solovyov, A. I., Pasechnikova, N. V., Khromov, O. S., Konakhovich, N. F., Krasnopolsky, Yu. M.
19. Patent of Ukraine No. 111762. Method for removing pharmacologically active liposomal dose, which contains quercetin. Grigor’e va, G. S., Krasnopolsky, Yu. M., Konakhovich, N. F., Pasechnikova N. V.
20. Patent US No 12168018 B1. Grygorieva, G., Konakhovych, N., Krasno polsky, Y., Pylypenko, O., Prokho rov, V., Suvorova, Z., Yadlovsky, O. Pharmaco logically active liposomal composition comprising quercetin and zink. 2024.
21. Pylypenko, D. М., Grigoryeva, G. S., Konakhovych, N. F., Krasnopolsky, Yu. М. (2022). Influence of the lipid composiotion of the properties, technology and quality indicators of liposomal drug. Biotecnologia Acta, 15(5), 23–30. https://doi.org/10.15407/biotech15.05.024
22. Belik, G. V., Grigor’eva, G. S., Derimedvid, L. V. (2004). Features of liposomal form of quercetin on the doxorubicin model cardiomyopathies. Liki, 5–6, 60–64. (InUkrainian).
23. Antipova, S. V., Shepil, A. V., Ryabtseva, O. D. (2009). Experience with the use of lipoflavone to prevent the development of cardiac complications in patients with operable breast cancer receiving treatment with anthracyclines. Problems of modern medical science and education, 2, 44–45. (In Ukrainian).
24. Shchetinina, T. A., Shepil, A. V. (2008). Evaluation of the effectiveness of Lipoflavon or the prevention of cardiac complications in patients with operable breast cancer receiving anthracycline therapy. Ukrainskyi edychnyi almanakh, 11(5), 207–208. (In Ukrainian).
25. Suvorova, Z. S. (2024). Anti-fuse activety of the liposomal form quercetin. Pharmacology and medicinal toxicology, 18(3), 185–190. (In Ukrainian). https://doi.org/10.33250/18.03.185
26. Krasnopolsky, Yu. M., Pilipenko, D. M. (2023). Development of antigen delivery systems and paints based on artificial and natural lipid nanoparticles: liposomes and exosomes (monograph). Kharkiv: DrukarnyaMadrid, 179. (In Ukrainian).
27. Uzlenkova, N., Grygoryeva, A., Skorobogatova, N., KryvkoА., Leonova, I., Konakhovich, N., …, Yadlovsky, O. (2024). Radioprotective activity of the liposomal omposition of quercetin in acute radiation syndrome (experimental study). Ukrainian Journal of Radiology and Oncology, 32(2), 31-243. https://doi.org/10.46879/ukroj.2.2024.231-243
28. Aguayo-Morales, H., Poblano, J., Berlanga, L., Castillo-Tobías, I., Silva-Belmares, S. Y., Cobos-Puc, L. E. (2024). Plant Antioxidants: Therapeutic Potential in Cardiovascular Diseases. Compounds, 4(3), 479–502. https://doi.org/10.3390/compounds4030029
29. Rezaei-Sadabady, R., Eidi, A., Zarghami, N., Barzegar, A. (2016). Intracellular ROS protection efficiency and free radicalscavenging activity of quercetin and quercetin-encapsulated liposomes. Artificial cells, nanomedicine, and biotechnology, 44(1), 128–134. https://doi.org/10.3109/21691401.2014.926456
30. El-Emam, M. M. A., Alobaida, A., El-Sayed, M. M., Qelliny, M. R., Ibrahim, M., Khamis, T., …, Subaiea G. M. (2025). Development of quercetin-loaded liposomal nanocarriers for alleviation of gemcitabineinduced hepatotoxicity: Optimization, in vitro, and in-vivo evaluation. Journal of Drug Delivery Science and Technolog, 105, 10665. https://doi.org/10.1016/j.jddst.2025.106659
31. Yin, N., Pang, J., Liu, X. (2025). Exploration of the optimal concentration of quercetin liposome nanoparticles for the treatment of liver damage. BMC pharmacology & toxicology, 26(1), 112. https://doi.org/10.1186/s40360-025-00951-x
32. Zhang, Y., Gong, S., Liu, L., Shen, H., Liu, E., Pan, L., …, Huang, Y. (2023). Cyclodextrin-Coordinated Liposome-in-Gel for Transcutaneous Quercetin Delivery for Psoriasis Treatment. ACS applied materials & interfaces, 15(34), 40228–40240. https://doi.org/10.1021/acsami.3c07582
33. Sun, G., Wu, Y., Li, J., Yang, M., Xu, H., Li, Y., …, Kong, X. (2025). Quercetin liposomes conjugated with hyaluronidase: An efficient drug delivery system to block pancreatic cancer. Journal of controlled release : official journal of the Controlled Release Society, 382, 113642. https://doi.org/10.1016/j. jconrel.2025.113642
34. Turkekul, K., Erdogan, S. (2023). Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles. Journal of cancer prevention, 28(4), 160–174. https://doi.org/10.15430/JCP.2023.28.4.160
35. Rezaei-Sadabady, R., Eidi, A., Zarghami, N., Barzegar, A. (2016). Intracellular ROS rotection efficiency and free radicalscavenging activity of quercetin and quercetin-encapsulated liposomes. Artificial cells, nanomedicine, and biotechnology, 44(1), 128–134. https://doi.org/10.3109/21691401.2014.926456
36. Benjanuwattra, J., Chaiyawat, P.,Pruksakorn, D., Koonrungsesomboon, N. (2020). Therapeutic potential and molecular mechanisms of mycophenolic acid as an anticancer agent. European journal of
pharmacology, 887, 173580. https://doi.org/10.1016/j.ejphar.2020.173580
37. Patel, G., Thakur, N. S., Kushwah, V., Patil, M. D., Nile, S. H., Jain, S., …, Kai, G. (2020). Liposomal Delivery of Mycophenolic Acid With Quercetin for Improved Breast Cancer Therapy in SD Rats. Frontiers in bioengineering and biotechnology, 8, 631. https://doi.org/10.3389/fbioe.2020.00631
38. Elbeltagi, S., Abdel Shakor, A. B., Alharbi, H., Tawfeek, H. M., Aldosari, B. N., Eldin, Z., …, Abd El-Aal, M. (2024). Synergistic effects of quercetin-loaded CoFe2O4@Liposomes regulate DNA damage and apoptosis in MCF-7 cancer cells: based on biophysical magnetic hyperthermia. Drug development and industrial pharmacy, 50(6), 561–575. https://doi.org/10.1080/03639045.2024.2363231
39. Demirbolat, G. M., Erdoğan, Ö., Coşkun, G. P., Çevik, Ö. (2022). PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy. Turkish journal of chemistry, 46(4), 1011–1023. https://doi.org/10.55730/13000527.3411
40. Chen, K. T. J., Anantha, M., Leung, A. W. Y., Kulkarni, J. A., Militao, G. G. C., Wehbe, M., …, Bally, M. B. (2020). Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use. Drug delivery and translational research, 10(1), 202–215. https://doi.org/10.1007/s13346-019-00674-7
41. Tilawat, M., Bonde, S. (2023). Curcumin and quercetin loaded nanocochleates gelformulation for localized application in breast cancer therapy. Heliyon, 9(12), e22892. https://doi.org/10.1016/j.heliyon.2023.e22892
42. Sanoqrot, S., Abujamous L. (2019). pHsensetive polymeric nanoparticles of quercetin as a potential colon cancer targeted nanomedicine. Journal of Drug Delivery Science and Technology, 52, 670-676. https://doi.org/10.1016/j.jddst.2019.05.035
43. Tefas, L. R., Tomuţă, I., Achim, M., Vlase, L. (2015). Development and optimization of uercetin-loaded PLGA nanoparticles by experimental design. Clujul medical (1957), 88(2), 214–223. https://doi.org/10.15386/cjmed-418
44. Ren, K. W., Li, Y. H., Wu, G., Ren, J. Z., Lu, H. B., Li, Z. M., Han, X. W. (2017). Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells. International journal of oncology, 50(4), 1299–1311. https://doi.org/10.3892/ijo.2017.3886
45. Moibenko, O. O. (2002). New technologies cardioprotection. Journal of Physiology, 48(4), 85–87. (In Ukrainian).
46. Moibenko, O. O., Parkhomenko, A. N., Kozhukhov, S. N. (2003). Efficacy of a water-soluble form of quercetin (corvitin) in the treatment of acute coronary syndrome (with ST-segment activation). Journal of the National Academy of Medical Sciences of Ukraine, 9(2), 61–70. (In Ukrainian).
47. Parkhomenko, A. N., Kozhukhov, S. N. (2014). Results of an open-label, randomized study to evaluate the tolerability and efficacy of Corvitin in patients with congestive heart failure and left ventricular systolic dysfunction. Ukrainian Medical Journal, 4, 71–76. (In Ukrainian).
48. Porcu, E. P., Cossu, M., Rassu, G., Giunchedi, P., Cerri, G., Pourová, J., …, Gavini, E. (2018). Aqueous injection of quercetin: An approach for confirmation of its direct in vivo cardiovascular effects. International journal of pharmaceutics, 541(1–2), 224–233. https://doi.org/10.1016/j.ijpharm.2018.02.036
49. Sharma, S., Thukral, R., Singla, L. D., Sing la, N., Choudhury, D. (2025). ercetin-loaded solid lipid nanoparticles for enhanced anti-helminthic activity International Journal of Pharmaceutics, 672, 125308. https://doi.org/10.1016/j.ijpharm.2025.125308
50. Mohamed, J. M. M., Ahmad, F., El-Sherbiny, M., Al Mohaini, M. A., Venkatesan, K., Alrashdi, Y. B. A., …, El Deeb, S. (2024). Optimization and characterization of quercetin-loaded solid lipids nanoparticles for biomedical application in colorectal cancer. Cancer Nano, 15, 16. https://doi.org/10.1186/s12645-024-00249-3
51. Das, S. S., Hussain, A., Verma, P. R. P., Imam, S. S., Altamimi, M. A., Alshehri, S., Singh, S. K. (2020). Recent Advances in Liposomal Drug Delivery System of Quercetin for Cancer Targeting: A Mechanistic Approach. Current drug delivery, 17(10), 845–860. https://doi.org/10.2174/1567201817666200415112657
52. Chen, K., Rekep, M., Wei, W., Wu, Q., Xue, Q., Li, S., Tian, J., …, Liu, Y. (2018). Quercetin Prevents In Vivo and In Vitro Myocardial Hypertrophy Through the Proteasome-GSK-3 Pathway. Cardiovascular drugs and therapy, 32(1), 5–21. https://doi.org/10.1007/s10557-018-6771-4
53. Lin, X., Lin, C. H., Zhao, T., Zuo, D., Ye, Z., Liu, L., Lin, M. T. (2017). Quercetin protects against heat stroke-induced myocardial injury in male rats: Antioxidative and ntiinflammatory mechanisms. Chemicobiological interactions, 265, 47–54. https://doi.org/10.1016/j.cbi.2017.01.006
54. Liu, H., Guo, X., Chu, Y., Lu, S. (2014). Heart protective effects and mechanism of quercetin preconditioning on antimyocardial ischemia reperfusion (IR) injuries in rats. Gene, 545(1), 149–155. https://doi.org/10.1016/j.gene.2014.04.043
55. Liu, C., Cheng, X., Wu, Y., Xu, W., Xia, H., Jia, R., …, Cheng, Z. (2023). Antioxidant Activity of Quercetin-Containing Liposomesin-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema. Pharmaceuticals (Basel, Switzerland), 16(8), 1184. https://doi.org/10.3390/ph16081184
{/accordions}