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Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery

BACKGROUND: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated...

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Autores principales: Willis, Alexander J, Pernal, Sebastian P, Gaertner, Zachary A, Lakka, Sajani S, Sabo, Michael E, Creighton, Francis M, Engelhard, Herbert H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295537/
https://www.ncbi.nlm.nih.gov/pubmed/32606667
http://dx.doi.org/10.2147/IJN.S247985
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author Willis, Alexander J
Pernal, Sebastian P
Gaertner, Zachary A
Lakka, Sajani S
Sabo, Michael E
Creighton, Francis M
Engelhard, Herbert H
author_facet Willis, Alexander J
Pernal, Sebastian P
Gaertner, Zachary A
Lakka, Sajani S
Sabo, Michael E
Creighton, Francis M
Engelhard, Herbert H
author_sort Willis, Alexander J
collection PubMed
description BACKGROUND: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT). METHODS: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium–boron–iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance. RESULTS: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect. CONCLUSION: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.
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spelling pubmed-72955372020-06-29 Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery Willis, Alexander J Pernal, Sebastian P Gaertner, Zachary A Lakka, Sajani S Sabo, Michael E Creighton, Francis M Engelhard, Herbert H Int J Nanomedicine Original Research BACKGROUND: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT). METHODS: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium–boron–iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance. RESULTS: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect. CONCLUSION: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed. Dove 2020-06-11 /pmc/articles/PMC7295537/ /pubmed/32606667 http://dx.doi.org/10.2147/IJN.S247985 Text en © 2020 Willis et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Willis, Alexander J
Pernal, Sebastian P
Gaertner, Zachary A
Lakka, Sajani S
Sabo, Michael E
Creighton, Francis M
Engelhard, Herbert H
Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title_full Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title_fullStr Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title_full_unstemmed Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title_short Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery
title_sort rotating magnetic nanoparticle clusters as microdevices for drug delivery
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295537/
https://www.ncbi.nlm.nih.gov/pubmed/32606667
http://dx.doi.org/10.2147/IJN.S247985
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