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Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticlesстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: 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.
- Журнал: Pharmaceutics
- Том: 14
- Номер: 11
- Год издания: 2022
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 2333
- Номер статьи: 2333
- DOI: 10.3390/pharmaceutics14112333
- Аннотация: Abstract: Currently, molecular dynamics simulation is being widely applied to predict drug–polymerinteraction, and to optimize drug delivery systems. Our study describes a combination of in silicoand 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–polymerbinding energy along with encapsulation efficacy, drug release profile, and the derivatives’ chemicalstructure. We applied ICP-MS analysis, the MTT test, and hemolytic activity assay to evaluate drugloading, antitumor activity, and hemocompatibility of the formulated nanoparticles. The drug encapsulationefficacy varied from 0.2% to 1% and correlated with in silico modelling results. The PLGAnanoparticles revealed higher antitumor activity against A549 human non-small-cell lung carcinomacells compared to non-encapsulated carboplatin derivatives with IC50 values of 1.40–23.20 M and7.32–79.30 M, respectively; the similar cytotoxicity profiles were observed against H69 and MCF-7cells. The nanoparticles efficiently induced apoptosis in A549 cells. Thus, nanoparticles loaded withnovel carboplatin derivatives demonstrated high application potential for anticancer therapy due totheir efficacy and high hemocompatibility. Our results demonstrated the combination of in silico andin vitro methods applicability for the optimization of encapsulation and antitumor efficacy in noveldrug delivery systems design.
- Добавил в систему: Подругина Татьяна Александровна
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