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Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation

PURPOSE: To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. METHODS: Micelles of mPEG750-b-oligo(ɛ-caprolactone)(5) (mPEG750-b-OCL(5)) with a hydroxyl (OH...

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Autores principales: Hofman, Jan-Willem, Carstens, Myrra G., van Zeeland, Femke, Helwig, Conny, Flesch, Frits M., Hennink, Wim E., van Nostrum, Cornelus F.
Formato: Texto
Lenguaje:English
Publicado: Springer US 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515570/
https://www.ncbi.nlm.nih.gov/pubmed/18597164
http://dx.doi.org/10.1007/s11095-008-9590-7
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author Hofman, Jan-Willem
Carstens, Myrra G.
van Zeeland, Femke
Helwig, Conny
Flesch, Frits M.
Hennink, Wim E.
van Nostrum, Cornelus F.
author_facet Hofman, Jan-Willem
Carstens, Myrra G.
van Zeeland, Femke
Helwig, Conny
Flesch, Frits M.
Hennink, Wim E.
van Nostrum, Cornelus F.
author_sort Hofman, Jan-Willem
collection PubMed
description PURPOSE: To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. METHODS: Micelles of mPEG750-b-oligo(ɛ-caprolactone)(5) (mPEG750-b-OCL(5)) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg®). RESULTS: Micelles composed of mPEG750-b-OCL(5) with benzoyl and naphtoyl end groups had the highest loading capacity up to 30% (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. CONCLUSION: The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo.
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spelling pubmed-25155702008-08-14 Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation Hofman, Jan-Willem Carstens, Myrra G. van Zeeland, Femke Helwig, Conny Flesch, Frits M. Hennink, Wim E. van Nostrum, Cornelus F. Pharm Res Research Paper PURPOSE: To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. METHODS: Micelles of mPEG750-b-oligo(ɛ-caprolactone)(5) (mPEG750-b-OCL(5)) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg®). RESULTS: Micelles composed of mPEG750-b-OCL(5) with benzoyl and naphtoyl end groups had the highest loading capacity up to 30% (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. CONCLUSION: The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. Springer US 2008-07-03 2008 /pmc/articles/PMC2515570/ /pubmed/18597164 http://dx.doi.org/10.1007/s11095-008-9590-7 Text en © The Author(s) 2008 https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Paper
Hofman, Jan-Willem
Carstens, Myrra G.
van Zeeland, Femke
Helwig, Conny
Flesch, Frits M.
Hennink, Wim E.
van Nostrum, Cornelus F.
Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title_full Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title_fullStr Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title_full_unstemmed Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title_short Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
title_sort photocytotoxicity of mthpc (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515570/
https://www.ncbi.nlm.nih.gov/pubmed/18597164
http://dx.doi.org/10.1007/s11095-008-9590-7
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