Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds

Hybrid microparticles based on an iron core and an amphiphilic polymeric shell have been prepared to respond simultaneously to magnetic and ultrasonic fields and variation in the surrounding pH to trigger and modulate the delivery of doxorubicin. The microparticles have been developed in four steps:...

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Main Authors: Sergei S. Vlasov, Pavel S. Postnikov, Mikhail V. Belousov, Sergei V. Krivoshchekov, Mekhman S. Yusubov, Artem M. Guryev, Antonio Di Martino
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/10/12/4324
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author Sergei S. Vlasov
Pavel S. Postnikov
Mikhail V. Belousov
Sergei V. Krivoshchekov
Mekhman S. Yusubov
Artem M. Guryev
Antonio Di Martino
author_facet Sergei S. Vlasov
Pavel S. Postnikov
Mikhail V. Belousov
Sergei V. Krivoshchekov
Mekhman S. Yusubov
Artem M. Guryev
Antonio Di Martino
author_sort Sergei S. Vlasov
collection DOAJ
description Hybrid microparticles based on an iron core and an amphiphilic polymeric shell have been prepared to respond simultaneously to magnetic and ultrasonic fields and variation in the surrounding pH to trigger and modulate the delivery of doxorubicin. The microparticles have been developed in four steps: (i) synthesis of the iron core; (ii) surface modification of the core; (iii) conjugation with the amphiphilic poly(lactic acid)-grafted chitosan; and (iv) doxorubicin loading. The particles demonstrate spherical shape, a size in the range of 1–3 µm and surface charge that is tuneable by changing the pH of the environment. The microparticles demonstrate good stability in simulated physiological solutions and are able to hold up to 400 µg of doxorubicin per mg of dried particles. The response to ultrasound and the changes in the shell structure during exposure to different pH levels allows the control of the burst intensity and release rate of the payload. Additionally, the magnetic response of the iron core is preserved despite the polymer coat. In vitro cytotoxicity tests performed on fibroblast NIH/3T3 demonstrate a reduction in the cell viability after administration of doxorubicin-loaded microparticles compared to the administration of free doxorubicin. The application of ultrasound causes a burst in the release of the doxorubicin from the carrier, causing a decrease in cell viability. The microparticles demonstrate in vitro cytocompatibility and hemocompatibility at concentrations of up to 50 and 60 µg/mL, respectively.
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spelling doaj.art-46001648fac14dd098aac02c4a440be32023-11-20T04:47:43ZengMDPI AGApplied Sciences2076-34172020-06-011012432410.3390/app10124324Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive CompoundsSergei S. Vlasov0Pavel S. Postnikov1Mikhail V. Belousov2Sergei V. Krivoshchekov3Mekhman S. Yusubov4Artem M. Guryev5Antonio Di Martino6Central Scientific Research Laboratory, Siberian State Medical University (SibSMU), 634050 Tomsk, RussiaResearch School of Chemistry & Applied Biomedical Sciences, Tomsk Polytechnic University, Lenin Av. 30, 634050 Tomsk, RussiaResearch School of Chemistry & Applied Biomedical Sciences, Tomsk Polytechnic University, Lenin Av. 30, 634050 Tomsk, RussiaDepartment of Pharmaceutical Analysis, Siberian State Medical University (SibSMU), 634050 Tomsk, RussiaCentral Scientific Research Laboratory, Siberian State Medical University (SibSMU), 634050 Tomsk, RussiaCentral Scientific Research Laboratory, Siberian State Medical University (SibSMU), 634050 Tomsk, RussiaResearch School of Chemistry & Applied Biomedical Sciences, Tomsk Polytechnic University, Lenin Av. 30, 634050 Tomsk, RussiaHybrid microparticles based on an iron core and an amphiphilic polymeric shell have been prepared to respond simultaneously to magnetic and ultrasonic fields and variation in the surrounding pH to trigger and modulate the delivery of doxorubicin. The microparticles have been developed in four steps: (i) synthesis of the iron core; (ii) surface modification of the core; (iii) conjugation with the amphiphilic poly(lactic acid)-grafted chitosan; and (iv) doxorubicin loading. The particles demonstrate spherical shape, a size in the range of 1–3 µm and surface charge that is tuneable by changing the pH of the environment. The microparticles demonstrate good stability in simulated physiological solutions and are able to hold up to 400 µg of doxorubicin per mg of dried particles. The response to ultrasound and the changes in the shell structure during exposure to different pH levels allows the control of the burst intensity and release rate of the payload. Additionally, the magnetic response of the iron core is preserved despite the polymer coat. In vitro cytotoxicity tests performed on fibroblast NIH/3T3 demonstrate a reduction in the cell viability after administration of doxorubicin-loaded microparticles compared to the administration of free doxorubicin. The application of ultrasound causes a burst in the release of the doxorubicin from the carrier, causing a decrease in cell viability. The microparticles demonstrate in vitro cytocompatibility and hemocompatibility at concentrations of up to 50 and 60 µg/mL, respectively.https://www.mdpi.com/2076-3417/10/12/4324core–shell microparticlesultrasoundamphiphilic polymersmagnetic microparticlesdoxorubicin
spellingShingle Sergei S. Vlasov
Pavel S. Postnikov
Mikhail V. Belousov
Sergei V. Krivoshchekov
Mekhman S. Yusubov
Artem M. Guryev
Antonio Di Martino
Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
Applied Sciences
core–shell microparticles
ultrasound
amphiphilic polymers
magnetic microparticles
doxorubicin
title Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
title_full Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
title_fullStr Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
title_full_unstemmed Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
title_short Multiresponsive Hybrid Microparticles for Stimuli-Responsive Delivery of Bioactive Compounds
title_sort multiresponsive hybrid microparticles for stimuli responsive delivery of bioactive compounds
topic core–shell microparticles
ultrasound
amphiphilic polymers
magnetic microparticles
doxorubicin
url https://www.mdpi.com/2076-3417/10/12/4324
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