Hypothesis The anticancer drug doxorubicin hydrochloride (DX) shows a high solubility in aqueous media thanks to the positive charge in the ammonium group. This feature, however, affects the drug encapsulation in the hydrophobic domains of polymeric micelles (PMs) used for the targeted delivery of the drug. At basic pH, DX deprotonates but also acquires a negative charge in the phenolic groups of the anthracycline structure. Both the efficiency and the rate of encapsulation will be increased by choosing an appropriate pH such that the drug molecule is in neutral form. Experiments An optimal pH for the encapsulation of the DX in PMs based on commercial poloxamers and on the diblock copolymer methoxy-poly(ethylene glycol)17-b-poly(ε-caprolactone)9 was determined by fluorescence spectroscopy, following the time evolution of both the intensity ratio of the first and the second emission bands of DX and its fluorescence lifetime, both sensitive to the environment polarity. Intracellular delivery of PMs encapsulated drug was followed by Confocal Scanning Laser Microscopy (CSLM). Cell viability was assessed with the sulforhodamine B (SRB) assay. Findings By adjusting pH to 8.1 a high yield of incorporation of DX in the PMs was achieved coupled to an appreciable increase (one order of magnitude) in the drug encapsulation rate. In-vitro tests in selected cancer cell lines showed the slow release of the drug and a delay in the cytotoxic response in comparison to free DX as detected by CSLM and SRB assay. The proposed methodology paves the way for a greener, faster and more efficient encapsulation of DX in PMs.

Determination of the optimal pH for doxorubicin encapsulation in polymeric micelles / Desiderio, Lucrezia; Gjerde, Natalie Solfried; Tasca, Elisamaria; Galantini, Luciano; Llarena, Irantzu; Di Gianvincenzo, Paolo; Thongsom, Sunisa; Moya, Sergio E.; Giustini, Mauro. - In: JOURNAL OF COLLOID AND INTERFACE SCIENCE. - ISSN 0021-9797. - (2024). [10.1016/j.jcis.2024.03.101]

Determination of the optimal pH for doxorubicin encapsulation in polymeric micelles

Desiderio, Lucrezia
Investigation
;
Galantini, Luciano
Membro del Collaboration Group
;
Giustini, Mauro
Writing – Review & Editing
2024

Abstract

Hypothesis The anticancer drug doxorubicin hydrochloride (DX) shows a high solubility in aqueous media thanks to the positive charge in the ammonium group. This feature, however, affects the drug encapsulation in the hydrophobic domains of polymeric micelles (PMs) used for the targeted delivery of the drug. At basic pH, DX deprotonates but also acquires a negative charge in the phenolic groups of the anthracycline structure. Both the efficiency and the rate of encapsulation will be increased by choosing an appropriate pH such that the drug molecule is in neutral form. Experiments An optimal pH for the encapsulation of the DX in PMs based on commercial poloxamers and on the diblock copolymer methoxy-poly(ethylene glycol)17-b-poly(ε-caprolactone)9 was determined by fluorescence spectroscopy, following the time evolution of both the intensity ratio of the first and the second emission bands of DX and its fluorescence lifetime, both sensitive to the environment polarity. Intracellular delivery of PMs encapsulated drug was followed by Confocal Scanning Laser Microscopy (CSLM). Cell viability was assessed with the sulforhodamine B (SRB) assay. Findings By adjusting pH to 8.1 a high yield of incorporation of DX in the PMs was achieved coupled to an appreciable increase (one order of magnitude) in the drug encapsulation rate. In-vitro tests in selected cancer cell lines showed the slow release of the drug and a delay in the cytotoxic response in comparison to free DX as detected by CSLM and SRB assay. The proposed methodology paves the way for a greener, faster and more efficient encapsulation of DX in PMs.
2024
doxorubicin; polymeric micelles; drug-delivery; fluorescence
01 Pubblicazione su rivista::01a Articolo in rivista
Determination of the optimal pH for doxorubicin encapsulation in polymeric micelles / Desiderio, Lucrezia; Gjerde, Natalie Solfried; Tasca, Elisamaria; Galantini, Luciano; Llarena, Irantzu; Di Gianvincenzo, Paolo; Thongsom, Sunisa; Moya, Sergio E.; Giustini, Mauro. - In: JOURNAL OF COLLOID AND INTERFACE SCIENCE. - ISSN 0021-9797. - (2024). [10.1016/j.jcis.2024.03.101]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1706336
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