Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation...

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Autores principales:	Mariia R. Mollaeva, Nikita Yabbarov, Maria Sokol, Margarita Chirkina, Murad D. Mollaev, Artur Zabolotskii, Irina Seregina, Mikhail Bolshov, Alexander Kaplun, Elena Nikolskaya
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nanoparticles PLGA metalloporphyrins Box–Behnken design drug release kinetics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d4217c143c614d45b2cf599665d50cba
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spelling	oai:doaj.org-article:d4217c143c614d45b2cf599665d50cba2021-11-25T17:54:46ZOptimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles10.3390/ijms2222122611422-00671661-6596https://doaj.org/article/d4217c143c614d45b2cf599665d50cba2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12261https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety.Mariia R. MollaevaNikita YabbarovMaria SokolMargarita ChirkinaMurad D. MollaevArtur ZabolotskiiIrina SereginaMikhail BolshovAlexander KaplunElena NikolskayaMDPI AGarticlenanoparticlesPLGAmetalloporphyrinsBox–Behnken designdrug releasekineticsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12261, p 12261 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles PLGA metalloporphyrins Box–Behnken design drug release kinetics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	nanoparticles PLGA metalloporphyrins Box–Behnken design drug release kinetics Biology (General) QH301-705.5 Chemistry QD1-999 Mariia R. Mollaeva Nikita Yabbarov Maria Sokol Margarita Chirkina Murad D. Mollaev Artur Zabolotskii Irina Seregina Mikhail Bolshov Alexander Kaplun Elena Nikolskaya Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
description	The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety.
format	article
author	Mariia R. Mollaeva Nikita Yabbarov Maria Sokol Margarita Chirkina Murad D. Mollaev Artur Zabolotskii Irina Seregina Mikhail Bolshov Alexander Kaplun Elena Nikolskaya
author_facet	Mariia R. Mollaeva Nikita Yabbarov Maria Sokol Margarita Chirkina Murad D. Mollaev Artur Zabolotskii Irina Seregina Mikhail Bolshov Alexander Kaplun Elena Nikolskaya
author_sort	Mariia R. Mollaeva
title	Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
title_short	Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
title_full	Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
title_fullStr	Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
title_full_unstemmed	Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles
title_sort	optimization, characterization and pharmacokinetic study of meso-tetraphenylporphyrin metal complex-loaded plga nanoparticles
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d4217c143c614d45b2cf599665d50cba
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Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

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