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Nanoemulsions and nanocapsules loaded with Melaleuca alternifolia essential oil for sepsis treatment

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Abstract

Sepsis represents a complex clinical syndrome that results from a harmful host response to infection. The infections most associated with sepsis are pneumonia, intra-abdominal infection, and urinary tract infection. Tea tree oil (TTO) has shown high antibacterial activity; however, it exhibits low aqueous solubility and high volatility, which have motivated its nanoencapsulation. In this study, the performance of nanoemulsions (NE) and nanocapsules (NC) loaded with TTO was compared. These systems were prepared by spontaneous emulsification and nanoprecipitation methods, respectively. Poly-ε-caprolactone or Eudragit® RS100 were tested as polymers for NCs whereas Tween® 80 or Pluronic® F68 as surfactants in NE preparation. Pluronic® F68 and Eudragit® RS100 resulted in more homogeneous and stable nanoparticles. In accelerated stability studies at 4 and 25 °C, both colloidal suspensions (NC and NE) were kinetically stable. NCs showed to be more stable to photodegradation and less cytotoxic than NEs. After sepsis induction by the cecal ligation and puncture (CLP) model, both NE and NC reduced neutrophil infiltration into peritoneal lavage (PL) and kidneys. Moreover, the systems increased group thiols in the kidney and lung tissue and reduced bacterial growth in PL. Taken together, both systems showed to be effective against injury induced by sepsis; however, NCs should be prioritized due to advantages in terms of cytotoxicity and physicochemical stability.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors like to thank the LCME-UFSC for technical support during TEM analyses and the Laboratory of Applied Virology for performing the cytotoxicity assays. We would like to thank the Brazilian governmental agencies CNPq and CAPES for the financial support for this project and for the student scholarship, respectively.

Funding

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Postgraduate Program in Pharmacy (PGFAR), Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis, SC, Brazil

    Mariana Alves Battisti, Larissa Constantino, Débora Fretes Argenta, Flávio Henrique Reginatto, Thiago Caon & Angela Machado Campos

  2. Laboratory of Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of South Santa Catarina, Criciúma, Brazil

    Felipe Dal Pizzol

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  1. Mariana Alves Battisti
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  2. Larissa Constantino
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  5. Felipe Dal Pizzol
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  6. Thiago Caon
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Contributions

Mariana Alves Battisti: conceptualization, methodology, writing—original draft, investigation, and data curation; Larissa Constantino: methodology and data curation; Debora Fretes Argenta: writing—review and editing; Flávio Henrique Reginatto and Felipe Dal Pizzol: Supervision; Thiago Caon: result discussion and writing—review and editing; Angela Machado Campos: conceptualization, supervision, methodology, writing—review and editing, project administration, and funding acquisition. 

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Correspondence to Angela Machado Campos.

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In vivo studies were performed according to the National Institutes of Health guidelines and approved by the local ethics committee (protocol number: PP00963).

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Highlights

• Tea tree oil (TTO)-loaded nanocapsules were more stable than nanoemulsions.

• TTO-loaded nanocapsules were less cytotoxic than nanoemulsions.

• TTO-loaded NEs and NCs reduced neutrophil infiltration levels in peritoneal lavage.

• Both nanostructured systems reduced the bacterial growth in peritoneal lavage.

• Both nanoparticles increased group thiols in the kidney and lungs.

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Battisti, M.A., Constantino, L., Argenta, D.F. et al. Nanoemulsions and nanocapsules loaded with Melaleuca alternifolia essential oil for sepsis treatment. Drug Deliv. and Transl. Res. 14, 1239–1252 (2024). https://doi.org/10.1007/s13346-023-01458-w

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