Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells

Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells

Diogo Silva Pellosi,1,2,* Francesca Moret,3,* Aurore Fraix,4 Nino Marino,4 Sara Maiolino,2 Elisa Gaio,3 Noboru Hioka,1 Elena Reddi,3 Salvatore Sortino,4 Fabiana Quaglia2 1Research Nucleus of Photodynamic Therapy, Chemistry Department, State University of Maringá, Maringá, Braz...

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Autores principales: Pellosi DS, Moret F, Fraix A, Marino N, Maiolino S, Gaio E, Hioka N, Reddi E, Sortino S, Quaglia F
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2016
Materias:
Pluronic Micelles
Sorafenib
Chemotherapy
Photodynamic Therapy
Verteporfin
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/b77f3e1332d44c15b968dc0b119757cd
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spelling oai:doaj.org-article:b77f3e1332d44c15b968dc0b119757cd2021-12-02T07:48:11ZPluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells1178-2013https://doaj.org/article/b77f3e1332d44c15b968dc0b119757cd2016-09-01T00:00:00Zhttps://www.dovepress.com/pluronicreg-p123f127-mixed-micelles-delivering-sorafenib-and-its-combi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Diogo Silva Pellosi,1,2,* Francesca Moret,3,* Aurore Fraix,4 Nino Marino,4 Sara Maiolino,2 Elisa Gaio,3 Noboru Hioka,1 Elena Reddi,3 Salvatore Sortino,4 Fabiana Quaglia2 1Research Nucleus of Photodynamic Therapy, Chemistry Department, State University of Maringá, Maringá, Brazil; 2Drug Delivery Laboratory, Department of Pharmacy, University of Naples Federico II, Naples, 3Cell Biology Unit, Department of Biology, University of Padova, Padua, 4Laboratory of Photochemistry, Department of Drug Sciences, University of Catania, Catania, Italy *These authors contributed equally to this work Abstract: Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB–VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori. Keywords: Pluronic® micelles, sorafenib, chemotherapy, photodynamic therapy, verteporfinPellosi DSMoret FFraix AMarino NMaiolino SGaio EHioka NReddi ESortino SQuaglia FDove Medical PressarticlePluronic MicellesSorafenibChemotherapyPhotodynamic TherapyVerteporfinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4479-4494 (2016)
institution DOAJ
collection DOAJ
language EN
topic Pluronic Micelles
Sorafenib
Chemotherapy
Photodynamic Therapy
Verteporfin
Medicine (General)
R5-920
spellingShingle Pluronic Micelles
Sorafenib
Chemotherapy
Photodynamic Therapy
Verteporfin
Medicine (General)
R5-920
Pellosi DS
Moret F
Fraix A
Marino N
Maiolino S
Gaio E
Hioka N
Reddi E
Sortino S
Quaglia F
Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
description Diogo Silva Pellosi,1,2,* Francesca Moret,3,* Aurore Fraix,4 Nino Marino,4 Sara Maiolino,2 Elisa Gaio,3 Noboru Hioka,1 Elena Reddi,3 Salvatore Sortino,4 Fabiana Quaglia2 1Research Nucleus of Photodynamic Therapy, Chemistry Department, State University of Maringá, Maringá, Brazil; 2Drug Delivery Laboratory, Department of Pharmacy, University of Naples Federico II, Naples, 3Cell Biology Unit, Department of Biology, University of Padova, Padua, 4Laboratory of Photochemistry, Department of Drug Sciences, University of Catania, Catania, Italy *These authors contributed equally to this work Abstract: Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB–VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori. Keywords: Pluronic® micelles, sorafenib, chemotherapy, photodynamic therapy, verteporfin
format article
author Pellosi DS
Moret F
Fraix A
Marino N
Maiolino S
Gaio E
Hioka N
Reddi E
Sortino S
Quaglia F
author_facet Pellosi DS
Moret F
Fraix A
Marino N
Maiolino S
Gaio E
Hioka N
Reddi E
Sortino S
Quaglia F
author_sort Pellosi DS
title Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
title_short Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
title_full Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
title_fullStr Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
title_full_unstemmed Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
title_sort pluronic® p123/f127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/b77f3e1332d44c15b968dc0b119757cd
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