NAVIGATING THE VASCULAR FRONTIER: EXPLORING QUERCETIN-BASED DRUG DELIVERY STRATEGIES IN CARDIOVASCULAR THERAPY
Main Article Content
Keywords
Quercetin, Drug delivery systems, Nanoparticles, Cardiovascular therapy, Lipid-based nanoparticles, Polymer-based nanoparticles, Targeted ligand conjugation
Abstract
This comprehensive review delves into the utilization of quercetin-based drug delivery systems in cardiovascular therapy, with a primary focus on various nanoparticle strategies, including lipid-based, polymer-based, and other nanocarriers. The investigation aims to assess the potential of these systems in enhancing quercetin's bioavailability, stability, and overall efficacy. Key findings highlight the effectiveness of nanoparticles in targeted delivery to cardiovascular sites and their role in controlled release mechanisms.
Lipid-based nanoparticles play a pivotal role in addressing quercetin's solubility challenges, while their polymer-based counterparts offer adaptability and controlled release capabilities. The exploration extends to alternative nanocarriers such as silica-based and metal-based systems, as well as hybrid nanocarrier approaches. The review discusses various structures like micelles, vesicles, hydrogels, and scaffolds, each contributing to specialized roles in improving quercetin delivery. The strategic use of targeted ligand conjugation emerges as a method to enhance specificity in cardiovascular treatment.
Insights from preclinical animal studies shed light on the effectiveness and safety of quercetin delivery systems, providing a foundation for potential clinical applications. The examination of human trials emphasizes study design elements and outcomes. The review elucidates the mechanisms of quercetin in cardiovascular therapy, encompassing antioxidant, anti-inflammatory, and vasodilatory effects.
Identified challenges, including limitations in bioavailability and safety concerns, set the stage for future collaborative approaches. The review proposes multidisciplinary cooperation and patient-centered strategies to address challenges and expedite clinical translation. Future trends and innovations, such as nanotechnologies, personalized medicine, artificial intelligence, and biomimetic delivery systems, are explored, indicating a promising trajectory for precision in cardiovascular therapy.
In conclusion, optimizing quercetin's therapeutic potential, overcoming delivery challenges, and fostering collaborative strategies emerge as essential implications for advancing cardiovascular therapy.
References
2. Luo, M., R. Tian, and N. Lu, Quercetin inhibited endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice: critical roles for NADPH oxidase and heme oxygenase-1. Journal of Agricultural and Food Chemistry, 2020. 68(39): p. 10875-10883.
3. Jantan, I., et al., Dietary polyphenols suppress chronic inflammation by modulation of multiple inflammation-associated cell signaling pathways. The Journal of Nutritional Biochemistry, 2021. 93: p. 108634.
4. Dagher, O., et al., Therapeutic potential of quercetin to alleviate endothelial dysfunction in age-related cardiovascular diseases. Frontiers in cardiovascular medicine, 2021. 8: p. 220.
5. Deng, Q., et al., Therapeutic potential of quercetin as an antiatherosclerotic agent in atherosclerotic cardiovascular disease: a review. Evidence-Based Complementary and Alternative Medicine, 2020. 2020.
6. Papakyriakopoulou, P., et al., Potential pharmaceutical applications of quercetin in cardiovascular diseases. Pharmaceuticals, 2022. 15(8): p. 1019.
7. Joshi, A., et al., Systems biology in cardiovascular disease: a multiomics approach. Nature Reviews Cardiology, 2021. 18(5): p. 313-330.
8. Vandenberghe, D. and J. Albrecht, The financial burden of non-communicable diseases in the European Union: a systematic review. European Journal of Public Health, 2020. 30(4): p. 833-839.
9. Bucciarelli, V., et al., Depression pandemic and cardiovascular risk in the COVID-19 era and long COVID syndrome: gender makes a difference. Trends in cardiovascular medicine, 2022. 32(1): p. 12-17.
10. Mourad, O., et al., Modeling heart diseases on a chip: advantages and future opportunities. Circulation Research, 2023. 132(4): p. 483-497.
11. Zakir, M., et al., Cardiovascular complications of diabetes: from microvascular to macrovascular pathways. Cureus, 2023. 15(9).
12. Geremew, G., et al., Adherence to Lifestyle Modification Practices and Its Associated Factors Among Hypertensive Patients in Bahir Dar City Hospitals, North West Ethiopia. Integrated Blood Pressure Control, 2023: p. 111-122.
13. Hogervorst, S., et al., Scalability of effective adherence interventions for patients using cardiovascular disease medication: A realist synthesis‐inspired systematic review. British journal of clinical pharmacology, 2023. 89(7): p. 1996-2019.
14. Adhami, M., et al., Drug loaded implantable devices to treat cardiovascular disease. Expert Opinion on Drug Delivery, 2023. 20(4): p. 507-522.
15. Pedretti, R.F., et al., How to optimize the adherence to a guideline-directed medical therapy in the secondary prevention of cardiovascular diseases: a clinical consensus statement from the European Association of Preventive Cardiology. European journal of preventive cardiology, 2023. 30(2): p. 149-166.
16. Le, T.H., et al., Quercetin-incorporated collagen/chitosan/SiO2 composite toward the robust antioxidant biomaterials. International Journal of Polymeric Materials and Polymeric Biomaterials, 2023: p. 1-8.
17. Usman Abid, H.M., et al., Exploring the Potent Combination of Quercetin-Boronic Acid, Epalrestat, and Urea Containing Nanoethosomal Keratolytic Gel for the Treatment of Diabetic Neuropathic Pain: In Vitro and In Vivo Studies. Mol Pharm, 2023. 20(7): p. 3623-3631.
18. Shabir, I., et al., Promising bioactive properties of quercetin for potential food applications and health benefits: A review. Frontiers in nutrition, 2022. 9: p. 999752.
19. Nazari-Khanamiri, F. and M. Ghasemnejad-Berenji, Quercetin and Heart Health: From Molecular Pathways to Clinical Findings. Journal of Food Biochemistry, 2023. 2023.
20. Pytliak, M. and V. Vaník, Quercetin as a Possible Cardiovascular Agent. 2023.
21. Azeem, M., et al., An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: a review. Polym Bull (Berl), 2023. 80(1): p. 241-262.
22. Chiang, M.-C., T.-Y. Tsai, and C.-J. Wang, The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms. International Journal of Molecular Sciences, 2023. 24(7): p. 6328.
23. Aghababaei, F. and M. Hadidi, Recent advances in potential health benefits of quercetin. Pharmaceuticals, 2023. 16(7): p. 1020.
24. Zhou, Y., et al., Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders. Phytotherapy Research, 2023. 37(11): p. 4999-5016.
25. Azeem, M., et al., Enhanced antibacterial and antioxidant properties of chitosan-quercetin complex containing polycaprolactone microspheres for the treatment of gastroenteritis: An in-vitro and in-vivo analysis. Materials Today Communications, 2022. 31: p. 103780.
26. Yamagata, K., Onion quercetin inhibits vascular endothelial cell dysfunction and prevents hypertension. European Food Research and Technology, 2023: p. 1-13.
27. Aatif, M., Current understanding of polyphenols to enhance bioavailability for better therapies. Biomedicines, 2023. 11(7): p. 2078.
28. Alemzadeh, E., et al., Topical treatment of cutaneous leishmaniasis lesions using quercetin/Artemisia-capped silver nanoparticles ointment: Modulation of inflammatory response. Acta Tropica, 2022. 228: p. 106325.
29. Mohamed, N.A., et al., Recent developments in nanomaterials-based drug delivery and upgrading treatment of cardiovascular diseases. International Journal of Molecular Sciences, 2022. 23(3): p. 1404.
30. Mehboob, R., et al., Role of endothelial cells and angiotensin converting enzyme-II in COVID-19 and brain damages post-infection. Frontiers in Neurology, 2023. 14.
31. Alajangi, H.K., et al., Blood–brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders. Molecular Brain, 2022. 15(1): p. 1-28.
32. Wang, Y., et al., Development of innovative biomaterials and devices for the treatment of cardiovascular diseases. Advanced Materials, 2022. 34(46): p. 2201971.
33. Dewanjee, S., et al., Recent advances in flavonoid-based nanocarriers as an emerging drug delivery approach for cancer chemotherapy. Drug Discovery Today, 2023. 28(1): p. 103409.
34. Lohiya, G. and D.S. Katti, Carboxylated chitosan-mediated improved efficacy of mesoporous silica nanoparticle-based targeted drug delivery system for breast cancer therapy. Carbohydrate Polymers, 2022. 277: p. 118822.
35. Kaur, S., et al., Quercetin nanoformulations: recent advancements and therapeutic applications. Advances in Natural Sciences: Nanoscience and Nanotechnology, 2023. 14(3): p. 033002.
36. Attar, E.S., et al., Nano Drug Delivery Strategies for an Oral Bioenhanced Quercetin Formulation. European Journal of Drug Metabolism and Pharmacokinetics, 2023. 48(5): p. 495-514.
37. Črnivec, I.G.O., et al., Waste streams in onion production: bioactive compounds, quercetin and use of antimicrobial and antioxidative properties. Waste Management, 2021. 126: p. 476-486.
38. Al-Khayri, J.M., et al., Flavonoids as potential anti-inflammatory molecules: A review. Molecules, 2022. 27(9): p. 2901.
39. Hosseini, A., et al., Quercetin and metabolic syndrome: A review. Phytotherapy Research, 2021. 35(10): p. 5352-5364.
40. Lin, X., et al., Quercetin improves vascular endothelial function through promotion of autophagy in hypertensive rats. Life Sciences, 2020. 258: p. 118106.
41. Zhang, Y.-M., Z.-Y. Zhang, and R.-X. Wang, Protective mechanisms of quercetin against myocardial ischemia reperfusion injury. Frontiers in Physiology, 2020. 11: p. 956.
42. Mirsafaei, L., et al., Molecular and biological functions of quercetin as a natural solution for cardiovascular disease prevention and treatment. Plant Foods for Human Nutrition, 2020. 75: p. 307-315.
43. Alizadeh, S.R., N. Savadkouhi, and M.A. Ebrahimzadeh, Drug design strategies that aim to improve the low solubility and poor bioavailability conundrum in quercetin derivatives. Expert Opinion on Drug Discovery, 2023. 18(10): p. 1117-1132.
44. Arshad, I., et al., Multifunctional role of nanoparticles for the diagnosis and therapeutics of cardiovascular diseases. Environmental Research, 2023: p. 117795.
45. Weisany, W., et al., Targeted delivery and controlled released of essential oils using nanoencapsulation: A review. Advances in Colloid and Interface Science, 2022. 303: p. 102655.
46. Wadhwa, K., et al., New insights into quercetin nanoformulations for topical delivery. Phytomedicine Plus, 2022. 2(2): p. 100257.
47. Hädrich, G., et al., Lipid-based nanocarrier for quercetin delivery: system characterization and molecular interactions studies. Drug Development and Industrial Pharmacy, 2016. 42(7): p. 1165-1173.
48. Hanif, M., et al., Improved anti-inflammatory effect of curcumin by designing self-emulsifying drug delivery system. Drug Dev Ind Pharm, 2021. 47(9): p. 1432-1438.
49. Gaspar, D.P., et al., Targeted delivery of lipid nanoparticles by means of surface chemical modification. Current Organic Chemistry, 2017. 21(23): p. 2360-2375.
50. Nathiya, S., M. Durga, and D. Thiyagarajan, Quercetin, encapsulated quercetin and its application-a review. International Journal of Pharmacy and Pharmaceutical Sciences, 2014: p. 20-26.
51. Hoti, G., et al., Nutraceutical concepts and dextrin-based delivery systems. International Journal of Molecular Sciences, 2022. 23(8): p. 4102.
52. Soumya, R.S. and K.G. Raghu, Recent advances on nanoparticle-based therapies for cardiovascular diseases. Journal of Cardiology, 2023. 81(1): p. 10-18.
53. Rudrapal, M., et al., Nanodelivery of dietary polyphenols for therapeutic applications. Molecules, 2022. 27(24): p. 8706.
54. Qi, X., et al., Development of quercetin-loaded PVCL–PVA–PEG micelles and application in inhibiting tumor angiogenesis through the PI3K/Akt/VEGF pathway. Toxicology and applied pharmacology, 2022. 437: p. 115889.
55. Rathod, S., et al., Advances on nanoformulation approaches for delivering plant-derived antioxidants: A case of quercetin. International Journal of Pharmaceutics, 2022: p. 122093.
56. Lee, C.-S. and H.S. Hwang, Starch-Based Hydrogels as a Drug Delivery System in Biomedical Applications. Gels, 2023. 9(12): p. 951.
57. Dhasmana, A., et al., A Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair. Biomedicines, 2022. 10(12): p. 3157.
58. Rampin, A., et al., Recent advances in KEAP1/NRF2-targeting strategies by phytochemical antioxidants, nanoparticles, and biocompatible scaffolds for the treatment of diabetic cardiovascular complications. Antioxidants & Redox Signaling, 2022. 36(10): p. 707-728.
59. Kaur, N., et al., Small molecules as cancer targeting ligands: Shifting the paradigm. Journal of Controlled Release, 2023. 355: p. 417-433.
60. Dorostkar, H., et al., Reduction of Doxorubicin-Induced Cardiotoxicity by Co-Administration of Smart Liposomal Doxorubicin and Free Quercetin: In Vitro and In Vivo Studies. Pharmaceutics, 2023. 15(7): p. 1920.
61. Singh, S., et al., Unveiling the future of metabolic medicine: omics technologies driving personalized solutions for precision treatment of metabolic disorders. Biochemical and Biophysical Research Communications, 2023.
62. Pechanova, O., E. Dayar, and M. Cebova, Therapeutic potential of polyphenols-loaded polymeric nanoparticles in cardiovascular system. Molecules, 2020. 25(15): p. 3322.
63. Abid, S., et al., Unlocking the potential of phenyl boronic acid functionalized-quercetin nanoparticles: Advancing antibacterial efficacy and diabetic wound healing. Heliyon, 2024. 10(1).
64. Ranjbar, S., et al., Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles. Pharmaceutics, 2023. 15(7): p. 1944.
65. Maity, S., A. Acharyya, and A.S. Chakraborti, Flavonoid-based polymeric nanoparticles: A promising approach for cancer and diabetes treatment. European Polymer Journal, 2022: p. 111455.
66. Kudaibergen, D., et al., Silica-Based Advanced Nanoparticles For Treating Ischemic Disease. Tissue Engineering and Regenerative Medicine, 2023. 20(2): p. 177-198.
67. Gowthami, B., Harnessing Medicinal Plant Phytochemicals: Unveiling Pharmacological Potential and Novel Drug Delivery Strategies. International Journal of Research in Pharmaceutical Sciences and Technology, 2023. 4(1): p. 11-17.
68. Hesari, M., et al., Current advances in the use of nanophytomedicine therapies for human cardiovascular diseases. International journal of nanomedicine, 2021: p. 3293-3315.
69. Mukherjee, P., et al., Role of animal models in biomedical research: a review. Laboratory Animal Research, 2022. 38(1): p. 18.
70. Kozłowska, A. and D. Szostak-Węgierek, Targeting cardiovascular diseases by flavonols: An update. Nutrients, 2022. 14(7): p. 1439.
71. Zhou, Y., et al., Roles and mechanisms of quercetin on cardiac arrhythmia: A review. Biomedicine & Pharmacotherapy, 2022. 153: p. 113447.
72. Zhou, W., et al., Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2-VEGFC complex. International Immunopharmacology, 2023. 116: p. 109842.
73. Gui, Y., et al., Quercetin improves rapid endothelialization and inflammatory microenvironment in electrospun vascular grafts. Biomedical Materials, 2022. 17(6): p. 065007.
74. Dadkhah Tehrani, S., et al., The effects of phytochemicals on serum triglycerides in subjects with hypertriglyceridemia: A systematic review of randomized controlled trials. Phytotherapy Research, 2023.
75. Luo, X., et al., A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis. Redox Biology, 2022. 57: p. 102511.
76. McGuckin, M.B., et al., Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. Journal of Controlled Release, 2022. 345: p. 334-353.
77. Naik, G.G., et al., Phytopharmaceuticals and herbal drugs: prospects and safety issues in the delivery of natural products, in Phytopharmaceuticals and Herbal Drugs. 2023, Elsevier. p. 215-248.
78. Goswami, T. and A. Chaudhary, Synthesis of Curcumin-Quercetin Loaded Chitosan Nanoparticles for Antimicrobial and Anticancer Activity. 2023, Jaypee University of Information Technology, Solan, HP.
79. Mohammadiounotikandi, A., A Multidisciplinary approach to innovations in biomedical engineering for improved patient care and well-being. Archive of Biomedical Science and Engineering, 2023. 9(1): p. 001-009.
80. Harish, V., et al., Cutting-edge advances in tailoring size, shape, and functionality of nanoparticles and nanostructures: A review. Journal of the Taiwan Institute of Chemical Engineers, 2023. 149: p. 105010.
81. Xu, X., et al., Network pharmacology and experiment indicated that medicinal food homologous components play important roles in insomnia. Food Frontiers, 2023.
82. Alshawwa, S.Z., et al., Nanocarrier drug delivery systems: characterization, limitations, future perspectives and implementation of artificial intelligence. Pharmaceutics, 2022. 14(4): p. 883.
83. Tang, P., et al., Challenges and opportunities for improving the druggability of natural product: Why need drug delivery system? Biomedicine & Pharmacotherapy, 2023. 164: p. 114955.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Hafiz Muhammad Usman Abid
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan
College of Pharmacy, Tahseen Ahmad Cheema Institute, Bahawalpur 63100, Punjab, Pakistan
Muhammad Azeem
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan
Muhammad Qaiser
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan
Drug Testing Laboratory, Punjab, Multan, Pakistan
Maria Tabassum Faqeer
Drug Testing Laboratory, Punjab, Multan, Pakistan
Sobia Abid
Department of Zoology, Rahim Yar Khan campus, The Islamia University of Bahawalpur
Muhammad Shakil
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan
Accident and Emergency Department Government, Nishtar Hospital Multan, Punjab, Pakistan
Aisha Khadija
University College of Pharmacy, University of the Punjab, Lahore, Pakistan
Drug Testing Laboratory, Punjab, Multan, Pakistan
Sana Ronaq
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan
Bilal Ahmad Ghalloo
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan.
College of Pharmacy, Tahseen Ahmad Cheema Institute, Bahawalpur 63100, Punjab, Pakistan
Umair Khurshid
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan
Khalid Mahmood
Institute of Chemical Sciences, Bahauddin Zakariya University Multan, Pakistan
Muhammad Hanif
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan