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Xanthan gum-based hydrogel containing nanocapsules for cutaneous diphenyl diselenide delivery in melanoma therapy

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Summary

The aim of this study was to further evaluate the antitumoral effect of (PhSe)2-loaded polymeric nanocapsules (NC (PhSe)2) against a resistant melanoma cell line (SK-Mel-103) and develop a xanthan gum-based hydrogel intending the NC (PhSe)2 cutaneous application. For the in vitro evaluation, cells were incubated with free (PhSe)2 or NC (PhSe)2 (0.7–200 μM) and after 48 h the MTT assay, propidium iodide uptake (necrosis marker) and nitrite levels were assessed. The hydrogels were developed by thickening of the NC (PhSe)2 suspension or (PhSe)2 solution with xanthan gum and characterized in terms of average diameter, polydispersity index, pH, drug content, spreadability, rheological profiles and in vitro permeation in human skin. The results showed that NC (PhSe)2 provided a superior antitumoral effect in comparison to free (PhSe)2 (IC50 value of 47.43 μM and 65.05 μM, respectively) and increased the nitrite content. Both compound forms induced propidium iodide uptake, suggesting a necrosis-related pathway could be involved in the cytotoxic action of (PhSe)2. All hydrogels showed pH values around 7, drug content close to the theoretical values (5 mg/g) and mean diameter in the nanometric range. Besides, formulations were classified as non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor. Skin permeation studies revealed that the compound content was higher for the nano-based hydrogel in the dermis layer, demonstrating its superior permeation, achieved by the compound encapsulation. It is the first report on an adequate formulation development for cutaneous application of NC (PhSe)2 that could be used as an adjuvant treatment in melanoma therapy.

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References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. Ca-Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  PubMed  Google Scholar 

  2. World Health Organization (2017) Skin cancers https://www.who.int/uv/faq/skincancer/en/index1.html. Accessed 16 January 2019

  3. Sondak VK, Gibney GT (2014) indications and options for systemic therapy in melanoma. Surg Clin N Am 94(5):1049. https://doi.org/10.1016/j.suc.2014.07.007

    Article  PubMed  Google Scholar 

  4. Rigon RB, Oyafuso MH, Fujimura AT, Goncalez ML, do Prado AH, Gremiao MPD, Chorilli M (2015) nanotechnology-based drug delivery systems for melanoma antitumoral therapy: a review. Biomed Res Int. https://doi.org/10.1155/2015/841817

  5. Nogueira CW, Rocha JBT (2011) Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds. Arch Toxicol 85(11):1313–1359. https://doi.org/10.1007/s00204-011-0720-3

    Article  CAS  PubMed  Google Scholar 

  6. Rosa RM, Roesler R, Braga AL, Saffi J, Henriques JAP (2007) Pharmacology and toxicology of diphenyl diselenide in several biological models. Braz J Med Biol Res 40(10):1287–1304. https://doi.org/10.1590/S0100-879x2006005000171

    Article  CAS  PubMed  Google Scholar 

  7. Barbosa NBD, Nogueira CW, Guecheva TN, Bellinaso MD, Rocha JBT (2008) Diphenyl diselenide supplementation delays the development of N-nitroso-N-methylurea-induced mammary tumors. Arch Toxicol 82(9):655–663. https://doi.org/10.1007/s00204-007-0271-9

    Article  CAS  Google Scholar 

  8. Posser T, de Paula MT, Franco JL, Leal AS, Rocha JBT (2011) Diphenyl diselenide induces apoptotic cell death and modulates ERK1/2 phosphorylation in human neuroblastoma SH-SY5Y cells. Arch Toxicol 85(6):645–651

    Article  CAS  Google Scholar 

  9. Melo MT, de Oliveira IM, Grivicich I, Guecheva TN, Saffi J, Henriques JAP, Rosa RM (2013) Diphenyl diselenide protects cultured MCF-7 cells against tamoxifen-induced oxidative DNA damage. Biomed Pharmacother 67(4):329–335. https://doi.org/10.1016/j.biopha.2011.09.012

    Article  CAS  PubMed  Google Scholar 

  10. Nedel F, Campos VF, Alves D, McBride AJA, Dellagostin OA, Collares T, Savegnago L, Seixas FK (2012) Substituted diaryl diselenides: Cytotoxic and apoptotic effect in human colon adenocarcinoma cells. Life Sci 91(9–10):345–352. https://doi.org/10.1016/j.lfs.2012.07.023

    Article  CAS  PubMed  Google Scholar 

  11. Prigol M, Nogueira CW, Zeni G, Bronze MR, Constantino L (2013) Physicochemical and biochemical profiling of diphenyl diselenide. Appl Biochem Biotechnol 169(3):885–893. https://doi.org/10.1007/s12010-012-0042-9

    Article  CAS  PubMed  Google Scholar 

  12. Frank LA, Contri RV, Beck RCR, Pohlmann AR, Guterres SS (2015) Improving drug biological effects by encapsulation into polymeric nanocapsules. Wires Nanomed Nanobi 7(5):623–639. https://doi.org/10.1002/wnan.1334

    Article  CAS  Google Scholar 

  13. Basha M (2018) Nanotechnology as a promising strategy for anticancer drug delivery. Curr Drug Deliv 15(4):497–509. https://doi.org/10.2174/1567201814666170516114411

    Article  CAS  PubMed  Google Scholar 

  14. Friberg S, Nystrom AM (2015) Nanotechnology in the war against cancer: new arms against an old enemy - a clinical view. Future Oncol 11(13):1961–1975. https://doi.org/10.2217/Fon.15.91

    Article  CAS  PubMed  Google Scholar 

  15. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55(1):R1–R4. https://doi.org/10.1016/0378-5173(89)90281-0

    Article  CAS  Google Scholar 

  16. Brigger I, Dubernet C, Couvreur P (2002) Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54(5):631–651. https://doi.org/10.1016/S0169-409x(02)00044-3

    Article  CAS  PubMed  Google Scholar 

  17. Giordani CFA, de Souza D, Dornelles L, Nogueira CW, Alves MP, Prigol M, Rodrigues OED (2014) Diphenyl diselenide-loaded nanocapsules: preparation and biological distribution. Appl Biochem Biotechnol 172(2):755–766. https://doi.org/10.1007/s12010-013-0554-y

    Article  CAS  PubMed  Google Scholar 

  18. Stefanello ST, Dobrachinski F, de Carvalho NR, Amaral GP, Barcelos RP, Oliveira VA, Oliveira CS, Giordani CFA, Pereira ME, Rodrigues OED, Soares FAA (2015) Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects. Int J Nanomedicine 10. https://doi.org/10.2147/Ijn.S87190

  19. Ferreira LM, Cervi VF, Sari MHM, Barbieri AV, Ramos AP, Copetti PM, de Brum GF, Nascimento R, Nadal JM, Farago PV, Sagrillo MR, Nogueira CW, Cruz L (2018) Diphenyl diselenide loaded poly(epsilon-caprolactone) nanocapsules with selective antimelanoma activity: Development and cytotoxic evaluation. Mat Sci Eng C-Mater 91:1–9. https://doi.org/10.1016/j.msec.2018.05.014

    Article  CAS  Google Scholar 

  20. Redpath M, Marques CMG, Dibden C, Waddon A, Lalla R, MacNeil S (2009) Ibuprofen and hydrogel-released ibuprofen in the reduction of inflammation-induced migration in melanoma cells. Brit J Dermatol 161(1):25–33. https://doi.org/10.1111/j.1365-2133.2009.09220.x

    Article  CAS  Google Scholar 

  21. Li J, Wang YJ, Liang RJ, An XJ, Wang K, Shen GX, Tu YT, Zhu JT, Tao J (2015) Recent advances in targeted nanoparticles drug delivery to melanoma. Nanomed-Nanotechnol 11(3):769–794. https://doi.org/10.1016/j.nano.2014.11.006

    Article  CAS  Google Scholar 

  22. Sisti A, Sisti G, Oranges CM (2015) Topical treatment of melanoma skin metastases with Imiquimod: a review. Dermatol Online J 21(2):1–9

    Google Scholar 

  23. Guterres SS, Alves MP, Pohlmann AR (2007) Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insights 2:147–157

    Article  Google Scholar 

  24. Alves MP, Scarrone AL, Santos M, Pohlmann AR, Guterres SS (2007) Human skin penetration and distribution of nimesulide from hydrophilic gels containing nanocarriers. Int J Pharm 341(1–2):215–220. https://doi.org/10.1016/j.ijpharm.2007.03.031

    Article  CAS  PubMed  Google Scholar 

  25. Marchiori MCL, Rascovetzki RH, Ourique AF, Rigo LA, Silva CB, Beck RCR (2013) Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness. Drug Dev Ind Pharm 39(4):579–586. https://doi.org/10.3109/03639045.2012.691510

    Article  CAS  PubMed  Google Scholar 

  26. Melero A, Ourique AF, Guterres SS, Pohlrnann AR, Lehr CM, Beck RCR, Schaefer U (2014) Nanoencapsulation in lipid-core nanocapsules controls mometasone furoate skin permeability rate and its penetration to the deeper skin layers. Skin Pharmacol Physiol 27(4):217–228. https://doi.org/10.1159/000354921

    Article  CAS  PubMed  Google Scholar 

  27. Rigo LA, da Silva CR, de Oliveira SM, Cabreira TN, da Silva CD, Ferreira J, Beck RCR (2015) Nanoencapsulation of rice bran oil increases its protective effects against UVB radiation-induced skin injury in mice. Eur J Pharm Biopharm 93:11–17. https://doi.org/10.1016/j.ejpb.2015.03.020

    Article  CAS  PubMed  Google Scholar 

  28. Flores FC, de Lima JA, da Silya CR, Benvegnu D, Ferreira J, Burger ME, Beck RCR, Rolim CMB, Rocha MIUM, da Veiga ML, da Silya CD (2015) Hydrogels containing nanocapsules and nanoemulsions of tea tree oil provide antiedematogenic effect and improved skin wound healing. J Nanosci Nanotechnol 15(1):800–809. https://doi.org/10.1166/jnn.2015.9176

    Article  CAS  PubMed  Google Scholar 

  29. Beber TC, de Andrade DF, Chaves PD, Pohlmann AR, Guterres SS, Beck RCR (2016) Cationic polymeric nanocapsules as a strategy to target dexamethasone to viable epidermis: skin penetration and permeation studies. J Nanosci Nanotechnol 16(2):1331–1338. https://doi.org/10.1166/jnn.2016.11670

    Article  CAS  PubMed  Google Scholar 

  30. de Andrade DF, Fontana MC, Pohlmann AR, Guterres SS, Beck RCR (2015) Nanoencapsulation of clobetasol propionate decreases its penetration to skin layers without changing its relative skin distribution. J Nanosci Nanotechnol 15(1):875–879. https://doi.org/10.1166/jnn.2015.9183

    Article  CAS  PubMed  Google Scholar 

  31. de Lima JA, Paines TC, Motta MH, Weber WB, dos Santos SS, Cruz L, da Silva CD (2017) Novel Pemulen/Pullulan blended hydrogel containing clotrimazole-loaded cationic nanocapsules: Evaluation of mucoadhesion and vaginal permeation. Mat Sci Eng C-Mater 79:886–893. https://doi.org/10.1016/j.msec.2017.05.030

    Article  CAS  Google Scholar 

  32. Pegoraro NS, Barbieri AV, Camponogara C, Mattiazzi J, Brum ES, Marchiori MCL, Oliveira SM, Cruz L (2017) Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice. Colloid Surface B 150:32–40. https://doi.org/10.1016/j.colsurfb.2016.11.013

    Article  CAS  Google Scholar 

  33. Marchiori MCL, Rigon C, Camponogara C, Oliveira SM, Cruz L (2017) Hydrogel containing silibinin-loaded pomegranate oil based nanocapsules exhibits anti-inflammatory effects on skin damage UVB radiation-induced in mice. J Photochem Photobiol B 170:25–32. https://doi.org/10.1016/j.jphotobiol.2017.03.015

    Article  CAS  PubMed  Google Scholar 

  34. Kumar A, Rao KM, Han SS (2018) Application of xanthan gum as polysaccharide in tissue engineering: A review. Carbohydr Polym 180:128–144. https://doi.org/10.1016/j.carbpol.2017.10.009

    Article  CAS  PubMed  Google Scholar 

  35. Paulmier C (1986) Selenoorganic functional groups. Selenium reagents and intermediates in organic synthesis. Angew Chem 100:25–51

    Google Scholar 

  36. Stuehr DJ, Nathan CF (1989) Nitric-oxide - a macrophage product responsible for cytostasis and respiratory inhibition in tumor target-cells. J Exp Med 169(5):1543–1555. https://doi.org/10.1084/jem.169.5.1543

    Article  CAS  PubMed  Google Scholar 

  37. Rigo LA, Weber J, Silva CB, Beck RCR (2012) Evaluation of the spreadability of pharmaceutical or cosmetic semisolid formulations using scanned images. Lat Am J Pharm 31(10):1387–1391

    CAS  Google Scholar 

  38. Drewes CC, Fiel LA, Bexiga CG, Asbahr ACC, Uchiyama MK, Cogliati B, Araki K, Guterres SS, Pohlmann AR, Farsky SP (2016) Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models. Int J Nanomedicine 11:1261–1279. https://doi.org/10.2147/Ijn.S101543

    Article  PubMed  PubMed Central  Google Scholar 

  39. Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6(7):521–534. https://doi.org/10.1038/nrc1910

    Article  CAS  PubMed  Google Scholar 

  40. Yarlagadda K, Hassani J, Foote IP, Markowitz J (2017) The role of nitric oxide in melanoma. Bba-Rev Cancer 1868(2):500–509. https://doi.org/10.1016/j.bbcan.2017.09.005

    Article  CAS  Google Scholar 

  41. Cevc G, Vierl U (2010) Nanotechnology and the transdermal route A state of the art review and critical appraisal. J Control Release 141(3):277–299. https://doi.org/10.1016/j.jconrel.2009.10.016

    Article  CAS  PubMed  Google Scholar 

  42. Fontana MC, JFP R, Coradini K, DBR L, RCR B (2011) Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate. Eur J Pharm Biopharm 79(2):241–249. https://doi.org/10.1016/j.ejpb.2011.05.002

    Article  CAS  PubMed  Google Scholar 

  43. Prajapati VD, Jani GK, Moradiya NG, Randeria NP (2013) Pharmaceutical applications of various natural gums, mucilages and their modified forms. Carbohydr Polym 92(2):1685–1699. https://doi.org/10.1016/j.carbpol.2012.11.021

    Article  CAS  PubMed  Google Scholar 

  44. Junyaprasert VB, Teeranachaideekul V, Souto EB, Boonme P, Müller RH (2009) Q10-loaded NLC versus nanoemulsions: Stability, rheology and in vitro skin permeation. Int J Pharm 377(1–2):207–214. https://doi.org/10.1016/j.ijpharm.2009.05.020

    Article  CAS  PubMed  Google Scholar 

  45. Rosseti IB, Rocha JBT, Costa MS (2015) Diphenyl diselenide (PhSe)(2) inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability. J Trace Elem Med Biol 29:289–295. https://doi.org/10.1016/j.jtemb.2014.08.001

    Article  CAS  PubMed  Google Scholar 

  46. Netto G, Jose J (2018) Development, characterization, and evaluation of sunscreen cream containing solid lipid nanoparticles of silymarin. J Cosmet Dermatol-Us 17(6):1073–1083. https://doi.org/10.1111/jocd.12470

    Article  Google Scholar 

  47. Garg A, Aggarwal D, Garg S, Singla AK (2002) Spreading of semisolid formulations. An Update. Pharm Technol 1:84–105

    Google Scholar 

  48. Contri RV, Katzer T, Ourique AF, da Silva ALM, Beck RCR, Pohlmann AR, Guterres SS (2014) Combined effect of polymeric nanocapsules and Chitosan hydrogel on the increase of capsaicinoids adhesion to the skin surface. J Biomed Nanotechnol 10(5):820–830. https://doi.org/10.1166/jbn.2014.1752

    Article  CAS  PubMed  Google Scholar 

  49. Singh S, Zafar A, Khan S, Naseem I (2017) Towards therapeutic advances in melanoma management: an overview. Life Sci 174:50–58. https://doi.org/10.1016/j.lfs.2017.02.011

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank Cristiane Bona da Silva for Zetasizer access.

Funding

We gratefully acknowledge UFSM, Fundo de Amparo à Pesquisa no Rio Grande do Sul (FAPERGS – 17/2551–0001041-8) and Coordenação de Aperfeiçoamento de Pessoal de nível Superior (CAPES-BR) for the financial support. Luana Mota Ferreira was granted a CAPES doctoral fellowship.

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Authors and Affiliations

  1. Laboratório de Tecnologia Farmacêutica, Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, 97105-900, Brazil

    Luana Mota Ferreira, Marcel Henrique Marcondes Sari, Verônica Ferrari Cervi, Marila Crivellaro Lay Marchiori & Letícia Cruz

  2. Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil

    Marcel Henrique Marcondes Sari & Cristina Wayne Nogueira

  3. Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde, Porto Alegre, Brazil

    Juliana Hofstatter Azambuja, Marcia Rosângela Wink, Jéssica Gonçalves Azevedo & Elizandra Braganhol

  4. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, Brazil

    Elita Ferreira da Silveira & Elizandra Braganhol

  5. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil

    Silvya Stuchi Maria-Engler

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  1. Luana Mota Ferreira
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Ferreira, L.M., Sari, M.H.M., Azambuja, J.H. et al. Xanthan gum-based hydrogel containing nanocapsules for cutaneous diphenyl diselenide delivery in melanoma therapy. Invest New Drugs 38, 662–674 (2020). https://doi.org/10.1007/s10637-019-00823-2

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