Skip to main content

Advertisement

SpringerLink
Log in

3-O-Methylquercetin from Achyrocline satureioides—cytotoxic activity against A375-derived human melanoma cell lines and its incorporation into cyclodextrins-hydrogels for topical administration

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

3-O-Methylquercetin (3OMQ), a natural 3-O-methylflavonoid, was isolated from Achyrocline satureioides and purified using the high-performance counter current chromatography (HPCCC) on a semi-preparative scale. High-purity 3OMQ (98%) was obtained with excellent recovery (81.8% (w/w)) and good yield (190 mg/100 g of plant). Isolated 3OMQ was evaluated against the A375 human amelanotic melanoma cancer cell line and A375-derived with different degrees of aggressiveness (A375-A7, A375-G10, and A375-PCDNA3). The results showed that 3OMQ reduced the cell viability of all strains, demonstrating time- and dose-dependent responses. 3OMQ was used to obtain hydrogels for the topical treatment of melanoma. Thus, 3OMQ was incorporated into hypromellose hydrogels with/without different cyclodextrins (CDs). The 3OMQ formulations showed permeation/retention in all skin layers, namely stratum corneum, epidermis, and dermis. A significant amount of 3OMQ was found in the replication site of the melanoma cells (epidermis and dermis). Altogether, these results demonstrate that 3OMQ can be isolated from Achyrocline satureioides by HPCCC on a semi-preparative scale and exhibit cytotoxic activity against melanoma cells. Its incorporation into an HPMC hydrogel containing HP-β-CD yielded a formulation with excellent technological and biopharmaceutical characteristics for evaluating the topical management of melanoma.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

Raw data were generated at Universidade Federal do Rio Grande do Sul. Derived data supporting the findings of this study are available from the corresponding author Bianchi and Bassani on request. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

References

  1. Erb P, Ji J, Wernli M, Kump E, Glaser A, Büchner SA. Role of apoptosis in basal cell and squamous cell carcinoma formation. Immunol Lett. 2005;100:68–72.

    Article  CAS  Google Scholar 

  2. Hearing VJ, Leong SPL. From melanocytes to melanoma. The progression to malignancy Melanoma Res. 2006;16:469–70.

    Article  Google Scholar 

  3. Shain AH, Bastian BC. From melanocytes to melanomas. Nat Rev Cancer. 2016;345–58.

  4. Costa MC, Abraham LS, Barcaui C. Lentigo maligno tratado com imiquimode tópico : o valor in clinical monitoring. An Bras Dermatol. 2011;An Bras De:792–4.

  5. Verga E, Chohan B, Verdolini R. malignant melanoma treated with topical imiquimod: a bespoke treatment that spared the amputation. Case Rep Dermatol. 2019;11:1–6.

    Article  Google Scholar 

  6. Verma A, Singh S, Kaur R, Jain UK. Topical gels as drug delivery systems: a review. Int J Pharm Sci Rev Res. 2013;23:374–82.

    Google Scholar 

  7. Boss C, Brenner E, Braumüller H, Wieder T, Röcken M. Senescence induction in metastatic melanoma during immunotherapy with interferon-alpha. J Invest Dermatol. 2014;134:S96.

    Article  Google Scholar 

  8. Schadendorf D, Akkooi ACJ Van, Berking C, Griewank KG, Gutzmer R, Hauschild A, et al. Melanoma. 2018;971–84.

  9. Vrijsen R, Everaert L, Van Hoof LM, Vlietinck AJ, Vanden Berghe DA, Boeyé A. The poliovirus-induced shut-off of cellular protein synthesis persists in the presence of 3-methylquercetin, a flavonoid which blocks viral protein and RNA synthesis. Antiviral Res. 1987;7:35–42.

    Article  CAS  Google Scholar 

  10. Carini J, Klamt F, Linck V. Flavonoids from Achyrocline satureioides : promising biomolecules for anticancer therapy. RSC Adv. 2014;4:3131–44.

    Article  CAS  Google Scholar 

  11. Rubio S, Quintana J, Eiroa JL, Triana J, Estévez F. Acetyl derivative of quercetin 3-methyl ether-induced cell death in human leukemia cells is amplified by the inhibition of ERK. Carcinogenesis. 2007;28:2105–13.

    Article  CAS  Google Scholar 

  12. Zhao S, Jiang Y, Zhao J, Li H, Yin X, Wang Y, et al. Quercetin-3-methyl ether inhibits esophageal carcinogenesis by targeting the AKT / mTOR / p70S6K and MAPK pathways. 2018;1540–52.

  13. Duo-Long D, Yuan-Yuan Z, Xiao-Fen C, Xin-Yi H, Shi-Lan F. Advances in application of high-speed countercurrent chromatography in separation and purification of flavonoids. Chinese J Anal Chem. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences; 2011;39:269–75.

  14. Sutherland I a. Recent progress on the industrial scale-up of counter-current chromatography. J Chromatogr A. 2007;1151:6–13.

  15. Berthod A, Ruiz-Angel MJ, Carda-Broch S. Elution-extrusion countercurrent chromatography. Use of the liquid nature of the stationary phase to extend the hydrophobicity window. Anal Chem. 2003;75:5886–94.

  16. Marston A, Hostettmann K. Developments in the application of counter-current chromatography to plant analysis. J Chromatogr A [Internet]. 2006;1112:181–94. Available from: http://www.sciencedirect.com/science/article/pii/S0021967305019370

  17. Bianchi SE, Kaiser S, Pittol V, Doneda E, De Souza KCB, Bassani VL. Semi-preparative isolation and purification of phenolic compounds from Achyrocline satureioides (Lam) D.C. by high-performance counter-current chromatography. Phytochem Anal [Internet]. 2019;30:182– 192. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pca.2803

  18. Bianchi SE, Machado BEK, Marília GC, Michelle MA, Dal L, Marques MS, et al. Coumestrol/hydroxypropyl-β-cyclodextrin association incorporated in hydroxypropyl methylcellulose hydrogel exhibits wound healing effect: in vitro and in vivo study. Eur J Pharm Sci Elsevier. 2018;119:179–88.

    Article  CAS  Google Scholar 

  19. Schwingel L, Fasolo D, Holzschuh M, Lula I, Sinisterra R, Koester L, et al. Association of 3-O-methylquercetin with β-cyclodextrin: complex preparation, characterization and ex vivo skin permeation studies. J Incl Phenom Macrocycl Chem. 2008;62:149–59.

    Article  CAS  Google Scholar 

  20. Bidone J, Bica VC, Petrovick PR, Simões CMO, Koester LS, Bassani VL, et al. Simultaneous quantification of flavonoids from achyrocline satureioides by a polar-reversed phase lc method -application to skin permeation/retention studies. Pharmazie. 2014;69:5–9.

    CAS  PubMed  Google Scholar 

  21. Pittol V, Ortega GG, Doneda E, Bianchi SE, Santos MC, Koetz M, et al. Box-Behnken design for extraction optimization followed by high performance countercurrent chromatography: production of a flavonoid-enriched fraction from achyrocline. PLANT MED. 2020.

  22. Bracalente C, Ibañez IL, Berenstein A, Notcovich C, Cerda MB, Klamt F, et al. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Upregulation of antioxidant genes correlates with regression of melanoma malignancy and with malignant progression when downregulated. Oncotarget. 2016;7:41154–71.

    Article  Google Scholar 

  23. Bracalente C, Salguero N, Notcovich C, Müller CB, da Motta LL, Klamt F, et al. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: reversion or promotion of malignancy by inducing melanogenesis or metastasis. Oncotarget. 2016;7:41142–53.

    Article  Google Scholar 

  24. Koch C, Reichling J, Kehm R, Sharaf MM, Zentgraf H, Schneele J, et al. Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive and thymidine-kinase-negative herpesviruses. J Pharm Pharmacol. 2008;60:1545–50.

    Article  CAS  Google Scholar 

  25. Iccvam. Recommended Test Method Protocol: Hen’s Egg Test – Chorioallantoic Membrane (HET-CAM) Test Method. ICCVAM Test Method Eval. Rep. 2010.

  26. Luepke NP. Hen’s egg chorioallantoic membrane test for irritation potential. Food Chem Toxicol. 1985;23:287–91.

    Article  CAS  Google Scholar 

  27. Pereira RL, Leites FI, Paese K, Sponchiado RM, Michalowski CB, Guterres SS, et al. Hydrogel containing adapalene- and dapsone-loaded lipid-core nanocapsules for cutaneous application: development, characterization, in vitro irritation and permeation studies. Drug Dev Ind Pharm. 2016;42:2001–8.

    Article  CAS  Google Scholar 

  28. Liebsch M, Spielmann H. INVITTOX Protocol No. 47: The HET-CAM Test. Berlin; 2002;1–8.

  29. Bojczuk M, Zyzelewicz D, Hodurek P. Centrifugal partition chromatography - a review of recent applications and some classic references. J Sep Sci Germany. 2017;40:1597–609.

    Article  CAS  Google Scholar 

  30. Costa F das N, Leitao GG. Strategies of solvent system selection for the isolation of flavonoids by countercurrent chromatography. J Sep Sci Germany. 2010;33:336–47.

  31. Vetter W, Müller M, Englert M, Hammann S. Chapter 10- Countercurrent chromatography—when liquid-liquid extraction meets chromatography. In: Poole CFBT-L-PE, editor. Handbooks Sep Sci [Internet]. Elsevier; 2020. p. 289–325. Available from: http://www.sciencedirect.com/science/article/pii/B9780128169117000104

  32. van Dooren AA, Müller BW. Purity determinations of drugs with differential scanning calorimetry (DSC)-a critical review. Int J Pharm. 1984;20:217–33.

    Article  Google Scholar 

  33. Ma K, Wang H, Zhao M, Xing J. Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry. Anal Chim Acta. 2009;650:227–33.

    Article  CAS  Google Scholar 

  34. Schwingel LC, Schwingel GO, Storch N, Barreto F, Bassani VL. 3-O-Methylquercetin from organic Nicotiana tabacum L. trichomes: influence of the variety, cultivation and extraction parameters. Ind Crops Prod [Internet]. 2014;55:56–62. Available from: http://www.sciencedirect.com/science/article/pii/S0926669014000752

  35. Yamauchi K, Mitsunaga T, Afroze SH, Uddin MN. Structure-activity relationships of methylquercetin on anti-migration and anti-proliferation activity in B16 melanoma cells. Anticancer Res Greece. 2017;37:1575–9.

    Article  CAS  Google Scholar 

  36. Yamauchi K, Mitsunaga T. Methylquercetins stimulate melanin biosynthesis in a three-dimensional skin model. J Nat Med [Internet]. 2018;72:563–9. Available from: https://doi.org/10.1007/s11418-018-1175-0

  37. Zhang E-H, Wang R-F, Guo S-Z, Liu B. An update on antitumor activity of naturally occurring chalcones. Evid Based Complement Alternat Med. United States; 2013;2013:815621.

  38. Bracalente C, Rinflerch AR, Ibañez IL, García FM, Volonteri V, Galimberti GN, et al. Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients. Oncotarget. 2018;9:24097–108.

    Article  Google Scholar 

  39. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature [Internet]. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2012;483:603. Available from: https://doi.org/10.1038/nature11003

  40. Zhang H-L, Si L-B, Zeng A, Long F, Qi Z, Zhao R, et al. MicroRNA-21 antisense oligonucleotide improves the sensitivity of A375 human melanoma cell to Cisplatin: An in vitro study. J Cell Biochem [Internet]. 2018;119:3129–41. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.26455

  41. Li J, Mottamal M, Li H, Liu K, Zhu F, Cho YY, et al. Quercetin-3-methyl ether suppresses proliferation of mouse epidermal JB6 p+ cells by targeting ERKs. Carcinogenesis. 2012;33:459–65.

    Article  Google Scholar 

  42. DePinto W, Chu XJ, Smith M, Packman K, Goelzer P, Lovey A, et al. In vitro and in vivo activity of R547: a potent selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther. 2006;5:2644–58.

    Article  CAS  Google Scholar 

  43. De Almeida VL, Leitão A, Barrett Reina LDC, Montanari CA, Donnici CL, Lopes MTP. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: Uma introdução. Quim Nova. 2005;28:118–29.

    Article  Google Scholar 

  44. Kumar ADN, Bevara GB, Kaja LK, Badana AK, Malla RR. Protective effect of 3-O-methyl quercetin and kaempferol from Semecarpus anacardium against H2O2 induced cytotoxicity in lung and liver cells. BMC Complement Altern Med. BMC Complementary and Alternative Medicine; 2016;16:376.

  45. Rubio S, Quintana J, López M, Eiroa JL, Triana J, Estévez F. Phenylbenzopyrones structure-activity studies identify betuletol derivatives as potential antitumoral agents. Eur J Pharmacol. 2006;548:9–20.

    Article  CAS  Google Scholar 

  46. Li J, Zhu F, Lubet RA, Luca A De, Grubbs C, Ericson ME, et al. Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G 2 / M arrest and apoptosis y. 2013;143:134–43.

  47. Kim SH, Yoo ES, Woo JS, Han SH, Lee JH, Jung SH, et al. Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation. Eur J Pharmacol Elsevier B.V.; 2019;860.

  48. Chen Q, Kang J, Fu C. The independence of and associations among apoptosis, autophagy, and necrosis. Signal Transduct Target Ther. Springer: US; 2018. p. 3.

    Google Scholar 

  49. Loftsson T, Masson M. Cyclodextrins in topical drug formulations: theory and practice. 2001;225:15–30.

    CAS  Google Scholar 

  50. Paper O. Full-body skin mapping for six biophysical parameters: baseline values at 16 anatomical sites in 125 human subjects. 2012;25–33.

  51. Proksch E. pH in nature , humans and skin. 2018;1–9.

  52. Barnes HA. A handbook of elementary rheology. Science 2011;80.

  53. Jansook P, Ogawa N, Loftsson T. Cyclodextrins : structure, physicochemical properties and pharmaceutical applications. Int J Pharm Elsevier. 2018;535:272–84.

    Article  CAS  Google Scholar 

  54. Loftsson T, Bodor N. Effects of 2-hydroxypropyl-beta-cyclodextrin on the aqueous solubility of drugs and transdermal delivery of 17 beta-estradiol. Acta Pharm Nord. 1989;1:185–94.

    CAS  PubMed  Google Scholar 

  55. Hashidzume A, Tomatsu I, Harada A. Interaction of cyclodextrins with side chains of water soluble polymers: A simple model for biological molecular recognition and its utilization for stimuli-responsive systems. Polymer (Guildf). Elsevier Ltd; 2006;47:6011–27.

  56. Nep EI, Conway BR. Mucoadhesive properties of compacts and gels. Trop J Pharm Res. 2011;10:393–401.

    CAS  Google Scholar 

  57. Venkatraman S, Gale R. Skin adhesives and skin adhesion 1. Transdermal drug delivery systems. 1998;19.

  58. Carvalho FC, Calixto G, Hatakeyama IN, Luz GM, Gremião MPD, Chorilli M. Rheological, mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems. Drug Dev Ind Pharm. 2013;39:1750–7.

    Article  CAS  Google Scholar 

  59. Nathiely F, Fachel S, Medeiros-neves B, Dal M, Silvestri R, Santos K, et al. Box-Behnken design optimization of mucoadhesive chitosan-coated nanoemulsions for rosmarinic acid nasal delivery — In vitro studies. Carbohydr Polym Elsevier. 2018;199:572–82.

    Article  Google Scholar 

  60. dos Santos MK, Kreutz T, Danielli LJ, De Marchi JGB, Pippi B, Koester LS, et al. A chitosan hydrogel-thickened nanoemulsion containing Pelargonium graveolens essential oil for treatment of vaginal candidiasis. J Drug Deliv Sci Technol. Elsevier B.V.; 2020;56:101527.

  61. Carvalho IM. Ciclodextrinas: novas aplicações. Dissertação de mestrado: Universidade fernando pessoa; 2013.

    Google Scholar 

  62. Hammoud Z, Khreich N, Auezova L, Fourmentin S. Cyclodextrin-membrane interaction in drug delivery and membrane structure maintenance. Int J Pharm Elsevier. 2019;564:59–76.

    Article  CAS  Google Scholar 

  63. Bowen JL, Heard CM. Film drying and complexation effects in the simultaneous skin permeation of ketoprofen and propylene glycol from simple gel formulations. Int J Pharm. 2006;307:251–7.

    Article  CAS  Google Scholar 

  64. Dias PH, Scopel M, Martiny S, Bianchi SE, Bassani VL, Zuanazzi JAS. Hydroxypropyl-beta-cyclodextrin-containing hydrogel enhances skin formononetin permeation/retention. England: J Pharm Pharmacol; 2018.

    Google Scholar 

  65. Williams IIIRO, Mahaguna V, Sriwongjanya M. Characterization of an inclusion complex of cholesterol and hydroxypropyl- b -cyclodextrin. Eur J Pharm Biopharm. 1998;46:355–60.

    Article  CAS  Google Scholar 

  66. Shaikh R, Raj Singh T, Garland M, Woolfson A, Donnelly R. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3:89–100.

    Article  CAS  Google Scholar 

  67. Chaves PDS, Frank LA, Frank AG, Pohlmann AR, Guterres SS, Beck RCR. Mucoadhesive properties of Eudragit®RS100, Eudragit®S100, and poly(ε-caprolactone) nanocapsules: influence of the vehicle and the mucosal surface. AAPS PharmSciTech. 2018;19:1637–46.

    Article  CAS  Google Scholar 

  68. Batista-duharte A, Murillo GJ, Betancourt JE, Oliver P, Damiana T. The hen’s egg test on chorioallantoic membrane: an alternative assay for the assessment of the irritating effect of vaccine adjuvants. Int J Toxicol. 2016;1–7.

  69. Vargas A, Zeisser-Labouèbe M, Lange N, Gurny R, Delie F. The chick embryo and its chorioallantoic membrane (CAM) for the in vivo evaluation of drug delivery systems. Adv Drug Deliv Rev. 2007;59:1162–76.

    Article  CAS  Google Scholar 

  70. Reis Mansur MCPP, Leitão SG, Cerqueira-Coutinho C, Vermelho AB, Silva RS, Presgrave OAF, et al. In vitro and in vivo evaluation of efficacy and safety of photoprotective formulations containing antioxidant extracts. Brazilian J Pharmacogn. Sociedade Brasileira de Farmacognosia; 2016;26:251–8.

  71. Borghetti GS, Lula IS, Sinisterra RD, Bassani VL. Quercetin/β-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture. 2009;10.

Download references

Acknowledgments

We thank to Dr. Ilio Montanari from Centro de Pesquisas Químicas e Biológicas e Agronômicas da Universidade de Campinas, SP, for suplying the Achyrocline satureioides inflorescences.

Funding

Financial support and scholarship were provided by the Brazilian government agencies (FAPERGS-RS, CAPES, CNPq). This study is also funded by the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (INCT-TM/CNPq/FAPESP-465458/2014-9), Agencia Nacional de Promoción Científica y Tecnológica, Argentina (Cooperación Internacional PICT-CABBIO 2014-0818 and PICT 2014-1557); MCTI/CNPQ/CBAB Cooperação Internacional em Biotecnologia, Brasil (465113/2014-1). F.K. received a fellowship from MCT/CNPq (306439/2014-0).

Author information

Authors and Affiliations

  1. Laboratório de Desenvolvimento Galênico, Programa de Pós-Graduação Em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 90610-000, Porto Alegre, RS, 2752-607, Brazil

    Eduarda Doneda, Sara Elis Bianchi, Vanessa Pittol, Tainá Kreutz & Valquiria Linck Bassani

  2. Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcelos, 90035-003, Anexo, Porto Alegre, RS, 2600, Brazil

    Juliete Nathali Scholl, Fabrício Figueiró & Fábio Klamt

  3. Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcelos, 90035-003, Anexo, Porto Alegre, RS, 2600, Brazil

    Fabrício Figueiró & Fábio Klamt

  4. Instituto de Nanociencia Y Nanotecnología Nodo Constituyentes, Comisión Nacional de Energía Atómica, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET) Av. General Paz 1499, B1650KNA, San Martín, Buenos Aires, CNEA, Argentina

    Irene L. Ibañez, Candelaria Bracalente & Hebe Durán

  5. Universidad Nacional de San Martin, Escuela de Ciencia Y Tecnología, Campus Miguelete, B1650KNA, Villa Lynch, Buenos Aires, Argentina

    Hebe Durán

Authors
  1. Eduarda Doneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Elis Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vanessa Pittol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tainá Kreutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliete Nathali Scholl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irene L. Ibañez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Candelaria Bracalente
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hebe Durán
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fabrício Figueiró
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fábio Klamt
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Valquiria Linck Bassani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ED, SEB, and VP performed 3OMQ isolation; ED, SEB, VP, JNS, and TK performed all pharmacological tests; ED, SEB, ILI, CB, FF, HD, VLB, and FK participated in the design of the manuscript, data analysis and interpretation, and in the writing process; VLB supervised the entire study in collaboration with FK and HD.

Corresponding authors

Correspondence to Sara Elis Bianchi or Valquiria Linck Bassani.

Ethics declarations

Competing interests

The authors declare that they have no conflicts of interest.

Consent for publication

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 480 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Doneda, E., Bianchi, S.E., Pittol, V. et al. 3-O-Methylquercetin from Achyrocline satureioides—cytotoxic activity against A375-derived human melanoma cell lines and its incorporation into cyclodextrins-hydrogels for topical administration. Drug Deliv. and Transl. Res. 11, 2151–2168 (2021). https://doi.org/10.1007/s13346-020-00882-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00882-6

Keywords

Search

Navigation