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Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques

[Image: see text] Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms...

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Autores principales: Gergely, Lea P., Yüceel, Çiğdem, İşci, Ümit, Spadin, Florentin S., Schneider, Lukas, Spingler, Bernhard, Frenz, Martin, Dumoulin, Fabienne, Vermathen, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410667/
https://www.ncbi.nlm.nih.gov/pubmed/37493236
http://dx.doi.org/10.1021/acs.molpharmaceut.3c00306
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author Gergely, Lea P.
Yüceel, Çiğdem
İşci, Ümit
Spadin, Florentin S.
Schneider, Lukas
Spingler, Bernhard
Frenz, Martin
Dumoulin, Fabienne
Vermathen, Martina
author_facet Gergely, Lea P.
Yüceel, Çiğdem
İşci, Ümit
Spadin, Florentin S.
Schneider, Lukas
Spingler, Bernhard
Frenz, Martin
Dumoulin, Fabienne
Vermathen, Martina
author_sort Gergely, Lea P.
collection PubMed
description [Image: see text] Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains (Pc1). (1)H NMR spectroscopy combined with UV–vis absorption and fluorescence spectroscopy revealed that Pc1 exists as a mixture of regioisomers in monomeric form in dimethyl sulfoxide but forms dimers in an aqueous buffer. PVP, polyethylene glycol castor oil (Kolliphor RH40), and three different triblock copolymers with varying proportions of polyethylene and polypropylene glycol units (termed P188, P84, and F127) were tested as micellar carriers for Pc1. (1)H NMR chemical shift analysis, diffusion-ordered spectroscopy, and 2D nuclear Overhauser enhancement spectroscopy was applied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibited the highest affinity for encapsulating Pc1 in the micellar core and resulted in intense Pc1 fluorescence emission as well as efficient singlet oxygen formation along with PVP. Among the triblock copolymers, efficiency in binding and dimer dissolution decreased in the order F127 > P84 > P188. PVP was a strong binder for Pc1. However, Pc1 molecules are rather surface-attached and exist as monomer and dimer mixtures. The results demonstrate that NMR combined with optical spectroscopy offer powerful tools to assess parameters like drug binding, localization sites, and dynamic properties that play key roles in achieving high host–guest compatibility. With the corresponding adjustments, polymeric micelles can offer simple and easily accessible drug delivery systems optimizing phthalocyanines’ properties as efficient photosensitizers.
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spelling pubmed-104106672023-08-10 Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques Gergely, Lea P. Yüceel, Çiğdem İşci, Ümit Spadin, Florentin S. Schneider, Lukas Spingler, Bernhard Frenz, Martin Dumoulin, Fabienne Vermathen, Martina Mol Pharm [Image: see text] Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains (Pc1). (1)H NMR spectroscopy combined with UV–vis absorption and fluorescence spectroscopy revealed that Pc1 exists as a mixture of regioisomers in monomeric form in dimethyl sulfoxide but forms dimers in an aqueous buffer. PVP, polyethylene glycol castor oil (Kolliphor RH40), and three different triblock copolymers with varying proportions of polyethylene and polypropylene glycol units (termed P188, P84, and F127) were tested as micellar carriers for Pc1. (1)H NMR chemical shift analysis, diffusion-ordered spectroscopy, and 2D nuclear Overhauser enhancement spectroscopy was applied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibited the highest affinity for encapsulating Pc1 in the micellar core and resulted in intense Pc1 fluorescence emission as well as efficient singlet oxygen formation along with PVP. Among the triblock copolymers, efficiency in binding and dimer dissolution decreased in the order F127 > P84 > P188. PVP was a strong binder for Pc1. However, Pc1 molecules are rather surface-attached and exist as monomer and dimer mixtures. The results demonstrate that NMR combined with optical spectroscopy offer powerful tools to assess parameters like drug binding, localization sites, and dynamic properties that play key roles in achieving high host–guest compatibility. With the corresponding adjustments, polymeric micelles can offer simple and easily accessible drug delivery systems optimizing phthalocyanines’ properties as efficient photosensitizers. American Chemical Society 2023-07-26 /pmc/articles/PMC10410667/ /pubmed/37493236 http://dx.doi.org/10.1021/acs.molpharmaceut.3c00306 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Gergely, Lea P.
Yüceel, Çiğdem
İşci, Ümit
Spadin, Florentin S.
Schneider, Lukas
Spingler, Bernhard
Frenz, Martin
Dumoulin, Fabienne
Vermathen, Martina
Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title_full Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title_fullStr Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title_full_unstemmed Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title_short Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques
title_sort comparing pvp and polymeric micellar formulations of a pegylated photosensitizing phthalocyanine by nmr and optical techniques
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410667/
https://www.ncbi.nlm.nih.gov/pubmed/37493236
http://dx.doi.org/10.1021/acs.molpharmaceut.3c00306
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