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Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles

Currently, molecular dynamics simulation is being widely applied to predict drug–polymer interaction, and to optimize drug delivery systems. Our study describes a combination of in silico and in vitro approaches aimed at improvement in polymer-based nanoparticle design for cancer treatment. We appli...

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Autores principales: Sokol, Maria B., Chirkina, Margarita V., Yabbarov, Nikita G., Mollaeva, Mariia R., Podrugina, Tatyana A., Pavlova, Anna S., Temnov, Viktor V., Hathout, Rania M., Metwally, Abdelkader A., Nikolskaya, Elena D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698263/
https://www.ncbi.nlm.nih.gov/pubmed/36365151
http://dx.doi.org/10.3390/pharmaceutics14112333
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author Sokol, Maria B.
Chirkina, Margarita V.
Yabbarov, Nikita G.
Mollaeva, Mariia R.
Podrugina, Tatyana A.
Pavlova, Anna S.
Temnov, Viktor V.
Hathout, Rania M.
Metwally, Abdelkader A.
Nikolskaya, Elena D.
author_facet Sokol, Maria B.
Chirkina, Margarita V.
Yabbarov, Nikita G.
Mollaeva, Mariia R.
Podrugina, Tatyana A.
Pavlova, Anna S.
Temnov, Viktor V.
Hathout, Rania M.
Metwally, Abdelkader A.
Nikolskaya, Elena D.
author_sort Sokol, Maria B.
collection PubMed
description Currently, molecular dynamics simulation is being widely applied to predict drug–polymer interaction, and to optimize drug delivery systems. Our study describes a combination of in silico and in vitro approaches aimed at improvement in polymer-based nanoparticle design for cancer treatment. We applied the PASS service to predict the biological activity of novel carboplatin derivatives. Subsequent molecular dynamics simulations revealed the dependence between the drug–polymer binding energy along with encapsulation efficacy, drug release profile, and the derivatives’ chemical structure. We applied ICP-MS analysis, the MTT test, and hemolytic activity assay to evaluate drug loading, antitumor activity, and hemocompatibility of the formulated nanoparticles. The drug encapsulation efficacy varied from 0.2% to 1% and correlated with in silico modelling results. The PLGA nanoparticles revealed higher antitumor activity against A549 human non-small-cell lung carcinoma cells compared to non-encapsulated carboplatin derivatives with IC(50) values of 1.40–23.20 µM and 7.32–79.30 µM, respectively; the similar cytotoxicity profiles were observed against H69 and MCF-7 cells. The nanoparticles efficiently induced apoptosis in A549 cells. Thus, nanoparticles loaded with novel carboplatin derivatives demonstrated high application potential for anticancer therapy due to their efficacy and high hemocompatibility. Our results demonstrated the combination of in silico and in vitro methods applicability for the optimization of encapsulation and antitumor efficacy in novel drug delivery systems design.
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spelling pubmed-96982632022-11-26 Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles Sokol, Maria B. Chirkina, Margarita V. Yabbarov, Nikita G. Mollaeva, Mariia R. Podrugina, Tatyana A. Pavlova, Anna S. Temnov, Viktor V. Hathout, Rania M. Metwally, Abdelkader A. Nikolskaya, Elena D. Pharmaceutics Article Currently, molecular dynamics simulation is being widely applied to predict drug–polymer interaction, and to optimize drug delivery systems. Our study describes a combination of in silico and in vitro approaches aimed at improvement in polymer-based nanoparticle design for cancer treatment. We applied the PASS service to predict the biological activity of novel carboplatin derivatives. Subsequent molecular dynamics simulations revealed the dependence between the drug–polymer binding energy along with encapsulation efficacy, drug release profile, and the derivatives’ chemical structure. We applied ICP-MS analysis, the MTT test, and hemolytic activity assay to evaluate drug loading, antitumor activity, and hemocompatibility of the formulated nanoparticles. The drug encapsulation efficacy varied from 0.2% to 1% and correlated with in silico modelling results. The PLGA nanoparticles revealed higher antitumor activity against A549 human non-small-cell lung carcinoma cells compared to non-encapsulated carboplatin derivatives with IC(50) values of 1.40–23.20 µM and 7.32–79.30 µM, respectively; the similar cytotoxicity profiles were observed against H69 and MCF-7 cells. The nanoparticles efficiently induced apoptosis in A549 cells. Thus, nanoparticles loaded with novel carboplatin derivatives demonstrated high application potential for anticancer therapy due to their efficacy and high hemocompatibility. Our results demonstrated the combination of in silico and in vitro methods applicability for the optimization of encapsulation and antitumor efficacy in novel drug delivery systems design. MDPI 2022-10-29 /pmc/articles/PMC9698263/ /pubmed/36365151 http://dx.doi.org/10.3390/pharmaceutics14112333 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sokol, Maria B.
Chirkina, Margarita V.
Yabbarov, Nikita G.
Mollaeva, Mariia R.
Podrugina, Tatyana A.
Pavlova, Anna S.
Temnov, Viktor V.
Hathout, Rania M.
Metwally, Abdelkader A.
Nikolskaya, Elena D.
Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title_full Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title_fullStr Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title_full_unstemmed Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title_short Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles
title_sort structural optimization of platinum drugs to improve the drug-loading and antitumor efficacy of plga nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698263/
https://www.ncbi.nlm.nih.gov/pubmed/36365151
http://dx.doi.org/10.3390/pharmaceutics14112333
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