Skip to content
2000
image of Evaluation of Pharmacokinetics, Toxicity, and In Vivo Anti-Ulcer Activity of Myricetin-Loaded Self-Nanoemulsifying Drug Delivery Systems

Abstract

Background

The bioavailability of a variety of drugs has been enhanced by the use of self-nanoemulsifying drug delivery systems (SNEDDS). Despite having several pharmacological effects, myricetin has limited bioavailability because of its poor solubility, which limits its use. Self-nanoemulsifying drug delivery systems (SNEDDS) have been developed to solve this issue.

Aim

The study aims to develop and characterize a self-nanoemulsifying drug delivery system (SNEDDS) of myricetin and evaluate its pharmacokinetics, toxicity, and anti-ulcer 
activity.

Materials and Methods

Myricetin-SNEDDS was formulated by solubility testing of myricetin in excipients, constructing a pseudo-ternary phase diagram and characterized using emulsification time, percent transmittance, thermodynamic stability, droplet size, polydispersity index and morphological characterization (TEM). Further acute oral toxicity study, pharmacokinetic parameters, antiulcer activity and anti-oxidant activity on stomach tissue for Myricetin-SNEDDS were evaluated.

Results

Tween 80 (surfactant), propylene glycol (co-surfactant) and olive oil (oil phase) were used to prepare myricetin-SNEDDS, which was then optimized according to droplet size and emulsification ability. The obtained Myricetin-SNEDDS ME1F2 with droplet size <100 nm and emulsification time 9s. Further evaluations showed that these Myricetin-SNEDDS have no toxicity and the pharmacokinetic study showed improved systemic drug absorption, which increases oral bioavailability. Myricetin-SNEDDS showed significant anti-ulcer activity and anti-oxidant activity on stomach tissue.

Conclusion

Myricetin's gastroprotective properties and anti-oxidative efficacy can be improved by SNEDDS, according to research, and it has a good probability of becoming a bioactive substance used as an anti-ulcer agent.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ddl/10.2174/0122103031372608250519104757
2025-05-22
2025-08-13

  • From This Site

    /content/journals/ddl/10.2174/0122103031372608250519104757
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Qian J. Meng H. Xin L. Xia M. Shen H. Li G. Xie Y. Self-nanoemulsifying drug delivery systems of myricetin: Formulation development, characterization, and in vitro and in vivo evaluation. Colloids Surf. B Biointerfaces 2017 160 101 109 10.1016/j.colsurfb.2017.09.020 28917148
    [Google Scholar]
  2. Godse S. Mohan M. Kasture V. Kasture S. Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats. Pharm. Biol. 2010 48 5 494 498 10.3109/13880200903188526 20645789
    [Google Scholar]
  3. Kataoka M. Yano K. Hamatsu Y. Masaoka Y. Sakuma S. Yamashita S. Assessment of absorption potential of poorly water-soluble drugs by using the dissolution/permeation system. Europ. J. Pharma. Biopharma. 2013 85 3 Pt B 1317 1324 10.1016/j.ejpb.2013.06.018
    [Google Scholar]
  4. Yao Y. Lin G. Xie Y. Ma P. Li G. Meng Q. Wu T. Preformulation studies of myricetin: A natural antioxidant flavonoid. Pharmazie 2014 69 1 19 26 24601218
    [Google Scholar]
  5. Dang Y. Lin G. Xie Y. Duan J. Ma P. Li G. Ji G. Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability. Drug Res. 2013 64 10 516 522 10.1055/s‑0033‑1363220 24357136
    [Google Scholar]
  6. Din F. Aman W. Ullah I. Qureshi O.S. Mustapha O. Shafique S. Zeb A. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int. J. Nanomedicine 2017 12 7291 7309 10.2147/IJN.S146315 29042776
    [Google Scholar]
  7. Pathak K. Raghuvanshi S. Oral bioavailability: Issues and solutions via nanoformulations. Clin. Pharmacokinet. 2015 54 4 325 357 10.1007/s40262‑015‑0242‑x 25666353
    [Google Scholar]
  8. Zhang L. Qi Z. Huang Q. Zeng K. Sun X. Li J. Liu Y.N. Imprinted-like biopolymeric micelles as efficient nanovehicles for curcumin delivery. Colloids Surf. B Biointerfaces 2014 123 15 22 10.1016/j.colsurfb.2014.08.033 25222139
    [Google Scholar]
  9. Karashima M. Kimoto K. Yamamoto K. Kojima T. Ikeda Y. A novel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies. Eur. J. Pharm. Biopharm. 2016 107 142 150 10.1016/j.ejpb.2016.07.006 27393561
    [Google Scholar]
  10. Tran T.H. Guo Y. Song D. Bruno R.S. Lu X. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. J. Pharm. Sci. 2014 103 3 840 852 10.1002/jps.23858 24464737
    [Google Scholar]
  11. Khan A.W. Kotta S. Ansari S.H. Sharma R.K. Ali J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: Design, characterization, in vitro and in vivo evaluation. Drug Deliv. 2015 22 4 552 561 10.3109/10717544.2013.878003 24512268
    [Google Scholar]
  12. Sharma S. Narang J.K. Ali J. Baboota S. Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model. Nanotechnology 2016 27 37 375101 10.1088/0957‑4484/27/37/375101 27491690
    [Google Scholar]
  13. Kollipara S. Gandhi R.K. Pharmacokinetic aspects and in vitro-in vivo correlation potential for lipid-based formulations. Acta Pharm. Sin. B 2014 4 5 333 349 10.1016/j.apsb.2014.09.001 26579403
    [Google Scholar]
  14. Narayanan M. Reddy K.M. Marsicano E. Peptic ulcer disease and helicobacter pylori infection. Mo. Med. 2018 115 3 219 224 30228726
    [Google Scholar]
  15. Yeo S.H. Yang C.H. Peptic ulcer disease associated with helico-bacter pylori infection Korean J. Gastroenterol. 2016 67 6 289 299 10.4166/kjg.2016.67.6.289
    [Google Scholar]
  16. Périco L.L. Emílio-Silva M.T. Ohara R. Rodrigues V.P. Bueno G. Barbosa-Filho J.M. Rocha L.R.M. Batista L.M. Hiruma-Lima C.A. Systematic analysis of monoterpenes: Advances and challenges in the treatment of peptic ulcer diseases. Biomolecules 2020 10 2 265 10.3390/biom10020265 32050614
    [Google Scholar]
  17. Pathak R. Chandra P. Bioactive compounds from myrica esculenta: Antioxidant insights and docking studies on h+k+-atpase and h2 receptor targets. Med. Chem. 2025 1 9 10.2174/0115734064366819250125070619
    [Google Scholar]
  18. Balakrishnan P. Lee B.J. Oh D.H. Kim J.O. Hong M.J. Jee J.P. Kim J.A. Yoo B.K. Woo J.S. Yong C.S. Choi H.G. Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS). Eur. J. Pharm. Biopharm. 2009 72 3 539 545 10.1016/j.ejpb.2009.03.001 19298857
    [Google Scholar]
  19. Lin T.C. Yang C.Y. Wu T.H. Tseng C.H. Yen F.L. Myricetin nanofibers enhanced water solubility and skin penetration for increasing antioxidant and photoprotective activities. Pharmaceutics 2023 15 3 906 10.3390/pharmaceutics15030906 36986766
    [Google Scholar]
  20. Morakul B. Teeranachaideekul V. Limwikrant W. Junyaprasert V.B. Dissolution and antioxidant potential of apigenin self nanoemulsifying drug delivery system (SNEDDS) for oral delivery. Sci. Rep. 2024 14 1 8851 10.1038/s41598‑024‑59617‑z 38632321
    [Google Scholar]
  21. Baloch J. Sohail M.F. Sarwar H.S. Kiani M.H. Khan G.M. Jahan S. Rafay M. Chaudhry M.T. Yasinzai M. Shahnaz G. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: in vitro and in vivo evaluation. Medicina 2019 55 5 210 10.3390/medicina55050210 31137751
    [Google Scholar]
  22. Yoo J.H. Shanmugam S. Thapa P. Lee E.S. Balakrishnan P. Baskaran R. Yoon S.K. Choi H.G. Yong C.S. Yoo B.K. Han K. Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein. Arch. Pharm. Res. 2010 33 3 417 426 10.1007/s12272‑010‑0311‑5 20361307
    [Google Scholar]
  23. Berkman M. Güleç K. Pseudo ternary phase diagrams: A practical approach for the area and centroid calculation of stable microemulsion regions. İstanbul. J. Pharm. 2021 51 1 42 49
    [Google Scholar]
  24. Vlaia L. Coneac G. Muţ A.M. Olariu I. Vlaia V. Anghel D.F. Maxim M.E. Dobrescu A. Hîrjău M. Lupuleasa D. Topical biocompatible fluconazole-loaded microemulsions based on essential oils and sucrose esters: Formulation design based on pseudo-ternary phase diagrams and physicochemical characterization. Processes 2021 9 1 144 10.3390/pr9010144
    [Google Scholar]
  25. Patel J. Kevin G. Patel A. Raval M. Sheth N. Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery. Int. J. Pharm. Investig. 2011 1 2 112 118 10.4103/2230‑973X.82431 23071930
    [Google Scholar]
  26. Yoo J. Baskaran R. Yoo B.K. Self-nanoemulsifying drug delivery system of lutein: Physicochemical properties and effect on bioavailability of warfarin. Biomol. Ther. 2013 21 2 173 179 10.4062/biomolther.2013.011 24009877
    [Google Scholar]
  27. Usta D.Y. Timur B. Teksin Z.S. Formulation development, optimization by Box-Behnken design, characterization, in vitro, ex-vivo, and in vivo evaluation of bosentan-loaded self-nanoemulsifying drug delivery system: A novel alternative dosage form for pulmonary arterial hypertension treatment. Eur. J. Pharm. Sci. 2022 174 106159 10.1016/j.ejps.2022.106159 35263632
    [Google Scholar]
  28. Rathore C. Hemrajani C. Sharma A.K. Gupta P.K. Jha N.K. Aljabali A.A.A. Gupta G. Singh S.K. Yang J.C. Dwivedi R.P. Dua K. Chellappan D.K. Negi P. Tambuwala M.M. Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: Optimization, characterization, pharmacokinetic, and hepatotoxicity studies. Drug Deliv. Transl. Res. 2023 13 1 292 307 10.1007/s13346‑022‑01193‑8 35831776
    [Google Scholar]
  29. Kazi M. Al-Swairi M. Ahmad A. Raish M. Alanazi F.K. Badran M.M. Khan A.A. Alanazi A.M. Hussain M.D. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitro and in vivo assessment. Front. Pharmacol. 2019 10 459 10.3389/fphar.2019.00459 31118895
    [Google Scholar]
  30. Izham M.M.N. Hussin Y. Aziz M.N.M. Yeap S.K. Rahman H.S. Masarudin M.J. Mohamad N.E. Abdullah R. Alitheen N.B. Preparation and characterization of self nano-emulsifying drug delivery system loaded with citraland its antiproliferative effect on colorectal cells in vitro. Nanomaterials 2019 9 7 1028 10.3390/nano9071028 31323842
    [Google Scholar]
  31. Priani S.E. Rahayu D.P. Maulana I.T. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of cod liver oil. Borneo J. Pharm. 2021 4 2 128 134 10.33084/bjop.v4i2.1942
    [Google Scholar]
  32. Syukri Y. Fitriani H. Pandapotan H. Nugroho B.H. Formulation, characterization and stability of ibuprofen-loaded self-nano emulsifying drug delivery system (SNEDDS). Indones. J. Pharm. 2019 30 2 105 10.14499/indonesianjpharm30iss2pp105‑113
    [Google Scholar]
  33. Kumar M. Chawla P.A. Faruk A. Chawla V. Solid self-nanoemulsifying drug delivery systems of nimodipine: Development and evaluation. Future J. Pharm. Sci. 2024 10 1 87 10.1186/s43094‑024‑00653‑x
    [Google Scholar]
  34. Zafar A. Yasir M. Alruwaili N.K. Imam S.S. Alsaidan O.A. Alshehri S. Ghoneim M.M. Alquraini A. Rawaf A. Ansari M.J. Sara U.V.S. Formulation of self-nanoemulsifying drug delivery system of cephalexin: Physiochemical characterization and antibacterial evaluation. Polymers 2022 14 5 1055 10.3390/polym14051055 35267877
    [Google Scholar]
  35. Inugala S. Eedara B.B. Sunkavalli S. Dhurke R. Kandadi P. Jukanti R. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation. Eur. J. Pharm. Sci. 2015 74 1 10 10.1016/j.ejps.2015.03.024
    [Google Scholar]
  36. Nasr A. Gardouh A. Ghorab M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics 2016 8 3 20 10.3390/pharmaceutics8030020 27355963
    [Google Scholar]
  37. No O.T. 423: Acute Oral Toxicity—OECD Guideline for the Testing of Chemicals. Paris, France OECD Publishing 2002
    [Google Scholar]
  38. Slaoui M. Fiette L. Histopathology procedures: From tissue sampling to histopathological evaluation. Methods Mol. Biol. 2011 691 69 82 10.1007/978‑1‑60761‑849‑2_4 20972747
    [Google Scholar]
  39. Imran M. Saeed F. Hussain G. Imran A. Mehmood Z. Gondal T.A. El-Ghorab A. Ahmad I. Pezzani R. Arshad M.U. Bacha U. Shariarti M.A. Rauf A. Muhammad N. Shah Z.A. Zengin G. Islam S. Myricetin: A comprehensive review on its biological potentials. Food Sci. Nutr. 2021 9 10 5854 5868 10.1002/fsn3.2513 34646551
    [Google Scholar]
  40. Ibrahim I.A.A. Hussein A.I. Muter M.S. Mohammed A.T. Al-Medhtiy M.H. Shareef S.H. Aziz P.Y. Agha N.F.S. Abdulla M.A. Effect of nano silver on gastroprotective activity against ethanol-induced stomach ulcer in rats. Biomed. Pharmacother. 2022 154 113550 10.1016/j.biopha.2022.113550 35994814
    [Google Scholar]
  41. Chandra P. Kaleem M. Sachan N. Pathak R. Alanazi A.S. Alsaif, NA Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm. J. 2023 31 11 101815 10.1016/j.jsps.2023.101815
    [Google Scholar]
  42. Sofi S.H. Nuraddin S.M. Amin Z.A. Al-Bustany H.A. Nadir M.Q. Gastroprotective activity of Hypericum perforatum extract in ethanol-induced gastric mucosal injury in Wistar rats: A possible involvement of H+/K+ ATPase α inhibition. Heliyon 2020 6 10 e05249 10.1016/j.heliyon.2020.e05249 33102861
    [Google Scholar]
  43. Saxena B. Singh S. Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease. Drug Discov. Ther. 2017 11 2 98 103 10.5582/ddt.2016.01081 28320982
    [Google Scholar]
  44. Zhou D. Yang Q. Tian T. Chang Y. Li Y. Duan L.R. Li H. Wang S.W. Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomed. Pharmacother. 2020 126 110075 10.1016/j.biopha.2020.110075 32179202
    [Google Scholar]
  45. Meng J. Chen T. Zhao Y. Lu S. Yu H. Chang Y. Chen D. Study of the mechanism of anti-ulcer effects of virgin coconut oil on gastric ulcer-induced rat model. Arch. Med. Sci. 2019 15 5 1329 1335 10.5114/aoms.2018.76943 31572481
    [Google Scholar]
  46. Sabiu S. Garuba T. Sunmonu T. Ajani E. Sulyman A. Nurain I. Balogun A. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin a nd Ficus exasperata. Toxicol. Rep. 2015 2 261 267 10.1016/j.toxrep.2015.01.002 28962358
    [Google Scholar]
  47. Danisman B. Cicek B. Yildirim S. Bolat I. Kantar D. Golokhvast K.S. Nikitovic D. Tsatsakis A. Taghizadehghalehjoughi A. Carnosic acid ameliorates indomethacin-induced gastric ulceration in rats by alleviating oxidative stress and inflammation. Biomedicines 2023 11 3 829 10.3390/biomedicines11030829 36979808
    [Google Scholar]
  48. Iqbal U. Malik A. Sial N.T. Mehmood M.H. Uttra A.M. Tulain U.R. Erum A. Fayyaz-ur-Rehman, M.; Welson, N.N.; Mahmoud, M.H.; Alexiou, A.; Papadakis, M.; El-Saber Bathia, G. Eucalyptol attenuates indomethacin-induced gastric ulcers in rats by modulating the ICAM-1, eNOS and COX/LOX pathways: Insights from in silico, in vitro and in vivo approaches. Food Chem. Toxicol. 2025 199 115319 10.1016/j.fct.2025.115319 39965739
    [Google Scholar]
  49. Yadav A. Khatoon R. Sharma A. Antiulcer activity of momordica dioica fruits, extract. World J. Pharm. Pharm. Sci. 2022 2 4 1 13
    [Google Scholar]
  50. Shetty A.K. Jangi A. Kurdi M.S. Yashaswini L. Evaluation of Gastric Contents and Volume After Ingestion of Apple Juice versus Pure Complex Carbohydrate Using Gastric Ultrasonography: A Randomised Clinical Study. J. Clin. Diagn. Res. 2023 17 10 UC22 UC26 10.7860/JCDR/2023/64023.18595
    [Google Scholar]
  51. Nawale S. Priyanka N. Das S. Raju G.M. Data of in vivo screening of antiulcer activity for methanolic extract of Vernonia elaeagnifolia DC. Data Brief 2019 23 103753 10.1016/j.dib.2019.103753 31406898
    [Google Scholar]
  52. Abduljabbar A. Abdullah F.O. Abdoulrahman K. Galali Y. Abdel I. Abdel Aziz Ibrahim I. Gastroprotective, biochemical, and acute toxicity effects of papaver decaisnei against ethanol-induced gastric ulcers in rats. Processes 2022 10
    [Google Scholar]
  53. Zhang J. Chen R. Yu Z. Xue L. Superoxide dismutase (SOD) and catalase (CAT) activity assay protocols for Caenorhabditis elegans. Bio Protoc. 2017 7 16 e2505 10.21769/BioProtoc.2505 34541169
    [Google Scholar]
  54. Hadwan M.H. Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochem. 2018 19 1 7 10.1186/s12858‑018‑0097‑5 30075706
    [Google Scholar]
  55. Batran A.R. Al-Bayaty F. Jamil Al-Obaidi M.M. Abdualkader A.M. Hadi H.A. Ali H.M. Abdulla M.A. In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats. PLoS One 2013 8 5 e64751 10.1371/journal.pone.0064751 23724090
    [Google Scholar]
  56. Rizzo M. Measurement of malondialdehyde as a biomarker of lipid oxidation in fish. Am. J. Anal. Chem. 2024 15 9 303 332 10.4236/ajac.2024.159020
    [Google Scholar]
  57. Tipple T.E. Rogers L.K. Methods for the determination of plasma or tissue glutathione levels. Methods Mol. Biol. 2012 889 315 324 10.1007/978‑1‑61779‑867‑2_20 22669674
    [Google Scholar]
  58. Jamialahmadi K. Amiri A.H. Zahedipour F. Faraji F. Karimi G. Protective Effects of Auraptene against Free Radical-Induced Erythrocytes Damage. J. Pharmacopuncture 2022 25 4 344 353 10.3831/KPI.2022.25.4.344 36628343
    [Google Scholar]
  59. Repetto M.G. Llesuy S.F. Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Braz. J. Med. Biol. Res. 2002 35 5 523 534 10.1590/S0100‑879X2002000500003 12011936
    [Google Scholar]
  60. Casa L.C. Villegas I. Alarcón de la Lastra C. Motilva V. Calero M.M.J. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J. Ethnopharmacol. 2000 71 1-2 45 53 10.1016/S0378‑8741(99)00174‑9 10904145
    [Google Scholar]
  61. Dursun H. Bilici M. Albayrak F. Ozturk C. Saglam M.B. Alp H.H. Suleyman H. Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue. BMC Gastroenterol. 2009 9 1 36 10.1186/1471‑230X‑9‑36 19457229
    [Google Scholar]
  62. Ayala A. Muñoz M.F. Argüelles S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev. 2014 2014 1 31 10.1155/2014/360438 24999379
    [Google Scholar]
/content/journals/ddl/10.2174/0122103031372608250519104757
Loading
Evaluation of Pharmacokinetics, Toxicity, and In Vivo Anti-Ulcer Activity of Myricetin-Loaded Self-Nanoemulsifying Drug Delivery Systems
Bentham Science Publishers ; https://doi.org/10.2174/0122103031372608250519104757
/content/journals/ddl/10.2174/0122103031372608250519104757
/content/journals/ddl/10.2174/0122103031372608250519104757
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: SNEDDs ; Myricetin ; anti-oxidant ; bioavailability ; anti-ulcer

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test