Tolvaptan-Loaded Tomato-Derived Nanovesicles: Characterization and Evaluation of Cytotoxicity, Wound Healing Potential and the Effects on Cyst Formation in Renal Cell Lines
Mammadova, Ramila; Pratiwi, Feby Wijaya; Fiume, Immacolata; Abdelrady, Eslam; Makieieva, Olha; Zucaro, Laura; Trepiccione, Francesco; Vainio, Seppo; Pocsfalvi, Gabriella (2025-05-17)
Dove Medical Press
17.05.2025
Mammadova R, Pratiwi FW, Fiume I, Abdelrady E, Makieieva O, Zucaro L, Trepiccione F, Vainio S, Pocsfalvi G. Tolvaptan-Loaded Tomato-Derived Nanovesicles: Characterization and Evaluation of Cytotoxicity, Wound Healing Potential and the Effects on Cyst Formation in Renal Cell Lines. Int J Nanomedicine. 2025;20:6253-6269 https://doi.org/10.2147/IJN.S498012
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© 2025 Mammadova et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
https://creativecommons.org/licenses/by-nc/4.0/
© 2025 Mammadova et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202505233884
https://urn.fi/URN:NBN:fi:oulu-202505233884
Tiivistelmä
Purpose:
Plant-derived nanovesicles (PDNVs) are promising candidates for next-generation drug delivery system due to their scalability, low cytotoxicity and immunogenicity, and efficient cellular uptake. Here, tomato fruit-derived PDNVs were loaded with tolvaptan, a vasopressin V2-receptor antagonist with the aim to reduce drug cytotoxicity, control drug release and to improve drug efficiency in vitro.
Methods:
Tolvaptan was encapsulated by extrusion and electroporation. Entrapment efficiency (EE%) and drug loading capacity (DLC%) were optimized by changing the drug-to-PDNV ratio and time-dependent drug release rate was evaluated at two different pH. Tolvaptan-loaded PDNVs were characterized using physiochemical and morphological methods. Cellular uptake of fluorescently labelled tolvaptan-loaded PDNVs was evaluated. The cytotoxicity and effects of tolvaptan-loaded PDNVs on cyst formation and cell migration were studied in different renal cell cultures.
Results:
Electroporation resulted in higher EE% and DLC% than extrusion for the encapsulation of tolvaptan into PDNVs. MDCK cells efficiently uptake tolvaptan-loaded PDNVs. The release of the tolvaptan was time and pH dependent. Enhanced cell proliferation, suppressed cyst growth, and altered cyst morphology compared with controls was observed. Migration assay demonstrated that tolvaptan-encapsulated PDNVs had a favourable effect on enhancing wound healing and cell migration in renal cells.
Conclusion:
Tolvaptan-loaded PDNVs show promising features as a natural next-generation nanoscale delivery system in vitro for time and pH-dependent release of hydrophobic drugs, such as tolvaptan.
Plant-derived nanovesicles (PDNVs) are promising candidates for next-generation drug delivery system due to their scalability, low cytotoxicity and immunogenicity, and efficient cellular uptake. Here, tomato fruit-derived PDNVs were loaded with tolvaptan, a vasopressin V2-receptor antagonist with the aim to reduce drug cytotoxicity, control drug release and to improve drug efficiency in vitro.
Methods:
Tolvaptan was encapsulated by extrusion and electroporation. Entrapment efficiency (EE%) and drug loading capacity (DLC%) were optimized by changing the drug-to-PDNV ratio and time-dependent drug release rate was evaluated at two different pH. Tolvaptan-loaded PDNVs were characterized using physiochemical and morphological methods. Cellular uptake of fluorescently labelled tolvaptan-loaded PDNVs was evaluated. The cytotoxicity and effects of tolvaptan-loaded PDNVs on cyst formation and cell migration were studied in different renal cell cultures.
Results:
Electroporation resulted in higher EE% and DLC% than extrusion for the encapsulation of tolvaptan into PDNVs. MDCK cells efficiently uptake tolvaptan-loaded PDNVs. The release of the tolvaptan was time and pH dependent. Enhanced cell proliferation, suppressed cyst growth, and altered cyst morphology compared with controls was observed. Migration assay demonstrated that tolvaptan-encapsulated PDNVs had a favourable effect on enhancing wound healing and cell migration in renal cells.
Conclusion:
Tolvaptan-loaded PDNVs show promising features as a natural next-generation nanoscale delivery system in vitro for time and pH-dependent release of hydrophobic drugs, such as tolvaptan.
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