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Vaterite microparticle-loaded methylene blue for photodynamic activity in macrophages infected with Leishmania braziliensis

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Abstract

Calcium carbonate (CaCO3) exhibits a variety of crystalline phases, including the anhydrous crystalline polymorphs calcite, aragonite, and vaterite. Develo** porous calcium carbonate microparticles in the vaterite phase for the encapsulation of methylene blue (MB) as a photosensitizer (PS) for use in photodynamic therapy (PDT) was the goal of this investigation. Using an adsorption approach, the PS was integrated into the CaCO3 microparticles. The vaterite microparticles were characterized by scanning electron microscopy (SEM) and steady-state techniques. The trypan blue exclusion method was used to measure the biological activity of macrophages infected with Leishmania braziliensis in vitro. The vaterite microparticles produced are highly porous, non-aggregated, and uniform in size. After encapsulation, the MB-loaded microparticles kept their photophysical characteristics. The carriers that were captured allowed for dye localization inside the cells. The results obtained in this study indicated that the MB-loaded vaterite microparticles show promising photodynamic activity in macrophages infected with Leishmania braziliensis.

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References

  1. Domingues, K. L. T. G., Tanoshi, C. A., Noma, I. H. Y., Carvalho, M. D. B., Aristides, S. M. A., Demarchi, I. G., Pedroso, R. B., & Lonardoni, M. V. C. (2022). Economic impact of hospitalizations due to leishmaniasis in southern Brazil. Research Society and Development, 11, e39211831139–e39211831149. https://doi.org/10.33448/rsd-v11i8.31139

    Article  Google Scholar 

  2. Sharma, R., Viana, S. M., Ng, D. K. P., Kolli, B. K., Chang, K. P., & de Oliveira, C. I. (2020). Photodynamic inactivation of Leishmania braziliensis doubly sensitized with uroporphyrin and diamino-phthalocyanine activates effector functions of macrophages in vitro. Scientific Reports, 10, 17065–17078. https://doi.org/10.1038/s41598-020-74154-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pal, M., Ejeta, I., Girma, A., Dave, K., & Dave, P. (2022). Etiology, clinical spectrum, epidemiology, diagnosis, public health significance and control of Leishmaniasis: A comprehensive review. Acta Scientific Microbiology, 5, 140–151. https://doi.org/10.31080/ASMI.2022.05.1066

    Article  Google Scholar 

  4. Tironi, F. C., Machado, G. U., Arruda, S. M., & Machado, P. R. L. (2021). Plantar ulcer as an atypical manifestation of cutaneous leishmaniasis. Anais Brasileiros de Dermatologia, 96, 352–354. https://doi.org/10.1016/j.abd.2020.06.015

    Article  PubMed  PubMed Central  Google Scholar 

  5. Anversa, L., Tiburcio, M. G. S., Richini-Pereira, V. B., & Ramirez, L. E. (2018). Leishmaniose humana no Brasil: Uma revisão geral. Revista da Associação Médica Brasileira, 64, 281–289. https://doi.org/10.1590/1806-9282.64.03.281

    Article  PubMed  Google Scholar 

  6. Sundar, S., & Chakravarty, J. (2015). An update on pharmacotherapy for leishmaniasis. Expert Opinion on Pharmacotherapy, 16, 237–252. https://doi.org/10.1517/14656566.2015.973850

    Article  CAS  PubMed  Google Scholar 

  7. Wijnant, G. J., Dumetz, F., Dirkx, L., Bulte, D., Cuypers, B., Bocxlaer, K. V., & Hendrickx, S. (2022). Tackling drug resistance and other causes of treatment failure in leishmaniasis. Frontiers in Tropical Diseases, 3, 1–23. https://doi.org/10.3389/fitd.2022.837460

    Article  Google Scholar 

  8. Vital-Fujii, D. G., & Baptista, M. S. (2021). Progress in the photodynamic therapy treatment of Leishmaniasis. Brazilian Journal of Medical and Biological Research, 54, e11570–e11580. https://doi.org/10.1590/1414-431X2021e11570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Varzandeh, M., Mohammadinejad, R., Esmaeilzadeh-Salestani, K., Dehshahri, A., Zarrabi, A., & Aghaei-Afshar, A. (2021). Photodynamic therapy for leishmaniasis: Recent advances and future trends. Photodiagnosis and Photodynamic Therapy, 36, 102609–102615. https://doi.org/10.1016/j.pdpdt.2021.102609

    Article  CAS  PubMed  Google Scholar 

  10. Correia, J. H., Rodrigues, J. A., Pimenta, S., Dong, T., & Yang, Z. (2021). Photodynamic therapy review: principles photosensitizers, applications, and future directions. Pharmaceutics, 13, 1332–1347. https://doi.org/10.3390/pharmaceutics13091332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021). Nanotechnology approaches for global infectious diseases. Nature Nanotechnology, 16, 369–384. https://doi.org/10.1038/s41565-021-00866-8

    Article  CAS  PubMed  Google Scholar 

  12. Tobin, E., & Brenner, S. (2021). Nanotechnology fundamentals applied to clinical infectious diseases and public health. Open Forum Infectious Diseases, 8, 1–10. https://doi.org/10.1093/ofid/ofab583

    Article  CAS  Google Scholar 

  13. Goonoo, N., Huët, M. A. L., Chummun, I., Karuri, N., Badu, K., Gimié, F., Bergrath, J., Schulze, M., Müller, M., & Bhaw-Luximon, A. (2022). Nanomedicine-based strategies to improve treatment of cutaneous leishmaniasis. Royal Society Open Science, 9, 220058–220085. https://doi.org/10.1098/rsos.220058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hernández, I. P., Montanari, J., Valdivieso, W., Morilla, M. J., Romero, E. L., & Escobar, P. (2012). In vitro phototoxicity of ultradeformable liposomes containing chloroaluminum phthalocyanine against new world Leishmania species. Photochemistry and Photobiology B: Biology, 117, 157–163. https://doi.org/10.1016/j.jphotobiol.2012.09.018

    Article  CAS  Google Scholar 

  15. Mukherjee, S., Pradhan, S., Ghosh, S., Sundar, S., Das, S., Mukherjee, B., & Roy, S. (2020). Short-course treatment with imipramine entrapped in squalene liposomes results in sterile cure of experimental visceral leishmaniasis induced by antimony resistant leishmania donovani with increased efficacy. Frontiers in Cellular and Infection Microbiology, 10, 1–10. https://doi.org/10.3389/fcimb.2020.595415

    Article  CAS  Google Scholar 

  16. Pinto, S. M. L., Muehlmann, L. A., Ojeda, L. L. M., Arias, A. M. V., Cordero, M. V. R., Santos, M. F. M. A., Azevedo, R. B., & Rivero, P. E. (2021). Nanoemulsions with chloroaluminium phthalocyanine and paromomycin for combined photodynamic and antibiotic therapy for cutaneous leishmaniasis. Infection and Chemotherapy, 53, 342–354. https://doi.org/10.3947/ic.2021.0010

    Article  CAS  Google Scholar 

  17. Saqib, M., Bhatti, A. S. A., Ahmad, N. M., Ahmed, N., Shahnaz, G., Lebaz, N., & Elaissari, A. (2020). Amphotericin B loaded polymeric nanoparticles for treatment of Leishmania infections. Nanomaterials, 10, 1152–1167. https://doi.org/10.3390/nano10061152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Khatami, M., Alijani, H. Q., Mousazadeh, F., Hashemi, N., Mahmoudi, Z., Darijani, S., Bamorovat, M., Keyhani, A., Abdollahpour-Alitappehe, M., & Borhani, F. (2020). Calcium carbonate nanowires: Greener biosynthesis and their leishmanicidal activity. RSC Advances, 10, 38063–38068. https://doi.org/10.1039/D0RA04503A

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sekkal, W., & Zaoui, A. (2013). Nanoscale analysis of the morphology and surface stability of calcium carbonate polymorphs. Scientific Reports, 3, 1587–1597. https://doi.org/10.1038/srep01587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shi, R. J., Lang, J. Q., Wang, T., Zhou, N., & Ma, M. G. (2022). Fabrication properties, and biomedical applications of calcium-containing cellulose-based composites. Frontiers in Bioengineering and Biotechnology, 10, 937266–937275. https://doi.org/10.3389/fbioe.2022.937266

    Article  PubMed  PubMed Central  Google Scholar 

  21. Popova, V., Poletaeva, Y., Pyshnaya, I., Pyshnyi, D., & Dmitrienko, E. (2021). Designing pH-dependent systems based on nanoscale calcium carbonate for the delivery of an antitumor drug. Nanomaterials, 11, 2794–2309. https://doi.org/10.3390/nano11112794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tessarolo, L. D., de Menezes, R. R. P. P. B., Mello, C. P., Lima, D. B., Magalhães, E. P., Bezerra, E. M., Sales, F. A. M., Barroso Neto, I. L., Oliveira, M. F., dos Santos, R. P., Albuquerque, E. L., Freire, V. N., & Martins, A. M. (2018). Nanoencapsulation of benznidazole in calcium carbonate increases its selectivity to Trypanosoma cruzi. Parasitology, 145, 1191–1198. https://doi.org/10.1017/S0031182018000197

    Article  CAS  PubMed  Google Scholar 

  23. Borrego-Sánchez, A., Sánchez-Espejo, R., Albertini, B., Passerini, N., Cerezo, P., Viseras, C., & Sainz-Díaz, C. I. (2019). Ground calcium carbonate as a low cost and biosafety excipient for solubility and dissolution improvement of praziquantel. Pharmaceutics, 11, 533–545. https://doi.org/10.3390/pharmaceutics11100533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jiang, J., Wu, Y., Chen, C., Wang, X., Zhao, H., Xu, S., Yang, C. C., & **ao, B. (2018). A novel route to prepare the metastable vaterite phase of CaCO3 from CaCl2 ethanol solution and Na2CO3 aqueous solution. Advanced Powder Technology, 29, 2416–2422. https://doi.org/10.1016/j.apt.2018.06.020

    Article  CAS  Google Scholar 

  25. Souza, E. F., Ambrósio, J. A. R., Pinto, B. C. S., Beltrame, M., Sakane, K. K., Pinto, J. G., Ferreira-Strixino, J., Gonçalves, E. P., & Simioni, A. R. (2020). Vaterite submicron particles designed for photodynamic therapy in cells. Photodiagnosis and Photodynamic Therapy, 31, 101913–101919. https://doi.org/10.1016/j.pdpdt.2020.101913

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, Y., Qiao, L., Yan, H., Zizak, I., Zaslansky, P., Li, Y., Qi, L., & Ma, Y. (2020). Vaterite microdisc mesocrystals exposing the (001) facet formed via transformation from proto-vaterite amorphous calcium carbonate. Crystal Growth & Design, 20, 3482–3492. https://doi.org/10.1021/acs.cgd.0c00259

    Article  CAS  Google Scholar 

  27. Dou, J., Zhao, F., Fan, W., Chen, Z., & Guo, X. (2020). Preparation of non-spherical vaterite CaCO3 particles by flash nano precipitation technique for targeted and extended drug delivery. Journal of Drug Delivery Science and Technology, 57(2020), 101768–110775. https://doi.org/10.1016/j.jddst.2020.101768

    Article  CAS  Google Scholar 

  28. Remya, K. P., Kim, S., & Kim, M. (2022). Surfactant-free hydrothermal fabrication of vaterite CaCO3 with hexagonal bipyramidal morphologies using seawater. Powder Technology, 410, 117865–117873. https://doi.org/10.1016/j.powtec.2022.117865

    Article  CAS  Google Scholar 

  29. Jensen, A. C. S., Birkedal, H., & Bertinetti, L. (2019). Co-incorporation of alkali metal ions during amorphous calcium carbonate precipitation and their stabilizing effect. Physical Chemistry Chemical Physics, 21, 13230–13233. https://doi.org/10.1039/C9CP02437A

    Article  CAS  PubMed  Google Scholar 

  30. Ashokan, A., Rajendran, V., Kumar, T. S., & Jayaraman, G. (2021). Process optimization for the rapid conversion of calcite into hydroxyapatite microspheres for chromatographic applications. Ceramics International, 47, 18575–18583. https://doi.org/10.1038/s41598-022-16579-4

    Article  CAS  Google Scholar 

  31. Beuvier, T., Calvignac, B., Delcroix, G. J. R., Tran, M. K., Kodjikian, S., Delorme, N., Bardeau, J. F., Gibaud, A., & Boury, F. (2011). Synthesis of hollow vaterite CaCO3 microspheres in supercritical carbon dioxide medium. Journal of Materials Chemistry, 26, 9757–9761. https://doi.org/10.1039/C1JM10770D

    Article  Google Scholar 

  32. Huang, Y., Cao, L., Parakhonskiy, B. V., & Skirtach, A. G. (2022). Hard, soft, and hard-and-soft drug delivery carriers based on CaCO3 and alginate biomaterials: synthesis properties, pharmaceutical applications. Pharmaceutics, 14, 909–951. https://doi.org/10.3390/pharmaceutics14050909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sun, R., Willhammar, T., Grape, E. S., Strømme, M., & Cheung, O. (2019). Mesoscale transformation of amorphous calcium carbonate to porous Vaterite microparticles with morphology control. Crystal Growth & Design, 19, 5075–5087. https://doi.org/10.1021/acs.cgd.9b00438

    Article  CAS  Google Scholar 

  34. Sun, R., Zhang, P., Bajnóczi, E. G., Neagu, A., Tai, C. W., Persson, I., Strømme, M., & Cheung, O. (2018). Amorphous calcium carbonate constructed from nanoparticle aggregates with unprecedented surface area and mesoporosity. ACS Applied Materials & Interfaces, 10, 21556–21564. https://doi.org/10.1021/acsami.8b03939

    Article  CAS  Google Scholar 

  35. Abeykoon, K. G. M. D., Dunuweera, S. P., Liyanage, D. N. D., & Rajapakse, R. M. G. (2020). Removal of fluoride from aqueous solution by porous Vaterite calcium carbonate nanoparticles. Materials Research Express, 7, 035009–0350020. https://doi.org/10.1088/2053-1591/ab7692

    Article  CAS  Google Scholar 

  36. Aoki, P. H. B., Volpati, D., Caetano, W., & Constantino, C. J. L. (2010). Study of the interaction between cardiolipin bilayers and methylene blue in polymer-based Layer-by-Layer and Langmuir films applied as membrane mimetic systems. Vibrational Spectroscopy, 54, 93–102. https://doi.org/10.1016/j.vibspec.2010.03.013

    Article  CAS  Google Scholar 

  37. Ovchinnikov, O. V., Evtukhova, A. V., Kondratenko, T. S., Smirnov, M. S., Khokhlov, V. Y., & Erina, O. V. (2016). Manifestation of intermolecular interactions in FTIR spectra of methylene blue molecules. Vibrational Spectroscopy, 86, 181–186. https://doi.org/10.1016/j.vibspec.2016.06.016

    Article  CAS  Google Scholar 

  38. Samyn, L. M., Babu, R. S., Devendiran, M., & Barros, A. L. F. (2021). One-step electropolymerization of methylene blue films on highly flexible carbon fiber electrode as supercapacitors. Micro and Nano Systems Letters, 9, 1–10. https://doi.org/10.1186/s40486-021-00130-7

    Article  Google Scholar 

  39. Wang, C., He, C., Tong, Z., Liu, X., Ren, B., & Zeng, F. (2006). Combination of adsorption by porous CaCO3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery. International Journal of Pharmaceutics, 308, 160–167. https://doi.org/10.1016/j.ijpharm.2005.11.004

    Article  CAS  PubMed  Google Scholar 

  40. Fernández-Pérez, A., & Marbán, C. (2020). Visible light spectroscopic analysis of methylene blue in water: What comes after dimer? ACS Omega, 5, 29801–29815. https://doi.org/10.1021/acsomega.0c03830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lakkakula, J. R., Kurapati, R., Tynga, I., Abrahamse, H., Raichur, A. M., & Krause, R. W. M. (2016). The mechanism of catalase loading into porous vaterite CaCO3 crystals by co-synthesis. RSC Advances, 6, 104537–104548. https://doi.org/10.1039/C7CP07836F

    Article  CAS  Google Scholar 

  42. Pinto, J. G., Marcolino, L. M. C., & Ferreira-Strixino, J. (2021). Photodynamic activity of Photogem® in Leishmania promastigotes and infected macrophages. Future Microbiology, 16, 95–106. https://doi.org/10.2217/fmb-2020-0019

    Article  CAS  PubMed  Google Scholar 

  43. Mauel, J., Jörg, S., & Baggiolini, M. (1984). Intracellular parasite killing induced by electron carriers. II. Correlation between parasite killing and the induction of oxidative events in macrophages. Molecular and Biochemical Parasitology, 13, 97–110.

    Article  CAS  PubMed  Google Scholar 

  44. de Oliveira, S., Trahamane, E. J. O., Monteiro, J., Santos, G. P., Crugeira, P., Oliveira, C., Neto, M. B., & Pinheiro, A. (2017). Leishmanicidal effect of antiparasitic photodynamic therapy-ApPDT on infected macrophages. Lasers in Medical Science, 32, 1959–1964. https://doi.org/10.1007/s10103-017-2292-9

    Article  PubMed  Google Scholar 

  45. Pinto, J. G., Martins, J. F. S., Pereira, A. H. C., Mittmann, J., Raniero, L. J., & Ferreira-Strixino, J. (2017). Evaluation of methylene blue as photosensitizer in promastigotes of Leishmania major and Leishmania braziliensis. Photodiagnosis and Photodynamic Therapy, 18, 325–330. https://doi.org/10.1016/j.pdpdt.2017.04.009

    Article  CAS  PubMed  Google Scholar 

  46. Aureliano, D. P., Lindoso, J. A. L., Soares, S. R. C., Takakura, C. F. H., Pereira, T. M., & Ribeiro, M. S. (2018). Cell death mechanisms in Leishmania amazonensis triggered by methylene blue-mediated antiparasitic photodynamic therapy. Photodiagnosis and Photodynamic Therapy, 23, 1–8.

    Article  CAS  PubMed  Google Scholar 

  47. Silva, E. P. D. O., Mittmann, J., Ferreira, V. T. P., Cardoso, M. A. G., & Beltrame, M. (2015). Photodynamic effects of zinc phthalocyanines on intracellular amastigotes of Leishmania amazonensis and Leishmania braziliensis. Lasers in Medical Science, 30, 347–354. https://doi.org/10.1007/s10103-014-1665-6

    Article  PubMed  Google Scholar 

  48. Fagundes, J., Sakane, K. K., Bhattacharjee, T., Pinto, J. G., Ferreira, I., Raniero, L. J., & Ferreira-Strixino, J. (2019). Evaluation of photodynamic therapy with methylene blue, by the fourier transform infrared spectroscopy (FT-IR) in Leishmania major-in vitro. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2017, 229–235. https://doi.org/10.1016/j.saa.2018.09.031

    Article  CAS  Google Scholar 

  49. Sakane, K. K., Bhattacharjee, T., Fagundes, J., Marcolino, L. M. M., Ferreira, I., Pinto, J. G., & Ferreira-Strixino, J. (2021). Biochemical changes in Leishmania braziliensis after photodynamic therapy with methylene blue assessed by the Fourier transform infrared spectroscopy. Lasers in Medical Science, 36, 821–827. https://doi.org/10.1007/s10103-020-03110-2

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge the financial support of the Brazilian agency FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) with project number 2018/18531-6.

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  1. Research and Development Institute—IPD, Vale do Paraíba University—UNIVAP, Av. Shishima Hifumi, 2911, São José Dos Campos, SP, CEP 12244-000, Brazil

    Vitor Luca Moura Marmo, Jéssica A. R. Ambrósio, Erika Peterson Gonçalves, Leandro José Raniero, Milton Beltrame Junior, Juliana G. Pinto, Juliana Ferreira-Strixino & Andreza R. Simioni

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Marmo, V.L.M., Ambrósio, J.A.R., Gonçalves, E.P. et al. Vaterite microparticle-loaded methylene blue for photodynamic activity in macrophages infected with Leishmania braziliensis. Photochem Photobiol Sci 22, 1977–1989 (2023). https://doi.org/10.1007/s43630-023-00426-0

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