Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin
Zhuoxuan Li,1 Tatyana Kovshova,2 Julia Malinovskaya,2 Julian Knoll,1 Saeed Shanehsazzadeh,1 Nadezhda Osipova,2 Anastasia Chernysheva,3 Pavel Melnikov,2 Svetlana Gelperina,2 Matthias G Wacker1 1National University of Singapore, Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, S...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2024-03-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/blood-nanoparticle-interactions-create-a-brain-delivery-superhighway-f-peer-reviewed-fulltext-article-IJN |
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| author | Li Z Kovshova T Malinovskaya J Knoll J Shanehsazzadeh S Osipova N Chernysheva A Melnikov P Gelperina S Wacker MG |
| author_facet | Li Z Kovshova T Malinovskaya J Knoll J Shanehsazzadeh S Osipova N Chernysheva A Melnikov P Gelperina S Wacker MG |
| author_sort | Li Z |
| collection | DOAJ |
| description | Zhuoxuan Li,1 Tatyana Kovshova,2 Julia Malinovskaya,2 Julian Knoll,1 Saeed Shanehsazzadeh,1 Nadezhda Osipova,2 Anastasia Chernysheva,3 Pavel Melnikov,2 Svetlana Gelperina,2 Matthias G Wacker1 1National University of Singapore, Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, Singapore; 2Dmitry Mendeleev University of Chemical Technology of Russia, Moscow, Russia; 3V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian Federation, Moscow, RussiaCorrespondence: Matthias G Wacker, Email matthias.g.wacker@nus.edu.sgPurpose: This study investigated the brain targeting mechanism of doxorubicin-loaded polybutyl cyanoacrylate (PBCA) nanoparticles, particularly their interactions with the blood-brain barrier (BBB). The BBB protects the brain from drugs in the bloodstream and represents a crucial obstacle in the treatment of brain cancer.Methods: An advanced computer model analyzed the brain delivery of two distinct formulations, Doxil® and surfactant-coated PBCA nanoparticles. Computational learning was combined with in vitro release and cell interaction studies to comprehend the underlying brain delivery pathways.Results: Our analysis yielded a surprising discovery regarding the brain delivery mechanism of PBCA nanoparticles. While Doxil® exhibited the expected behavior, accumulating in the brain through extravasation in tumor tissue, PBCA nanoparticles employed a unique and previously uncharacterized mechanism. They underwent cell hitchhiking, resulting in a remarkable more than 1000-fold increase in brain permeation rate compared to Doxil® (2.59 × 10− 4 vs 0.32 h− 1).Conclusion: The nonspecific binding to blood cells facilitated and intensified interactions of surfactant-coated PBCA nanoparticles with the vascular endothelium, leading to enhanced transcytosis. Consequently, the significant increase in circulation time in the bloodstream, coupled with improved receptor interactions, contributes to this remarkable uptake of doxorubicin into the brain. Keywords: BBB, brain targeting, CNS, modeling, doxorubicin, drug delivery |
| first_indexed | 2024-03-07T15:17:05Z |
| format | Article |
| id | doaj.art-7af80330c16c4112935d9b1aec07989f |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-07T15:17:05Z |
| publishDate | 2024-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-7af80330c16c4112935d9b1aec07989f2024-03-05T17:51:53ZengDove Medical PressInternational Journal of Nanomedicine1178-20132024-03-01Volume 192039205690911Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for DoxorubicinLi ZKovshova TMalinovskaya JKnoll JShanehsazzadeh SOsipova NChernysheva AMelnikov PGelperina SWacker MGZhuoxuan Li,1 Tatyana Kovshova,2 Julia Malinovskaya,2 Julian Knoll,1 Saeed Shanehsazzadeh,1 Nadezhda Osipova,2 Anastasia Chernysheva,3 Pavel Melnikov,2 Svetlana Gelperina,2 Matthias G Wacker1 1National University of Singapore, Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, Singapore; 2Dmitry Mendeleev University of Chemical Technology of Russia, Moscow, Russia; 3V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian Federation, Moscow, RussiaCorrespondence: Matthias G Wacker, Email matthias.g.wacker@nus.edu.sgPurpose: This study investigated the brain targeting mechanism of doxorubicin-loaded polybutyl cyanoacrylate (PBCA) nanoparticles, particularly their interactions with the blood-brain barrier (BBB). The BBB protects the brain from drugs in the bloodstream and represents a crucial obstacle in the treatment of brain cancer.Methods: An advanced computer model analyzed the brain delivery of two distinct formulations, Doxil® and surfactant-coated PBCA nanoparticles. Computational learning was combined with in vitro release and cell interaction studies to comprehend the underlying brain delivery pathways.Results: Our analysis yielded a surprising discovery regarding the brain delivery mechanism of PBCA nanoparticles. While Doxil® exhibited the expected behavior, accumulating in the brain through extravasation in tumor tissue, PBCA nanoparticles employed a unique and previously uncharacterized mechanism. They underwent cell hitchhiking, resulting in a remarkable more than 1000-fold increase in brain permeation rate compared to Doxil® (2.59 × 10− 4 vs 0.32 h− 1).Conclusion: The nonspecific binding to blood cells facilitated and intensified interactions of surfactant-coated PBCA nanoparticles with the vascular endothelium, leading to enhanced transcytosis. Consequently, the significant increase in circulation time in the bloodstream, coupled with improved receptor interactions, contributes to this remarkable uptake of doxorubicin into the brain. Keywords: BBB, brain targeting, CNS, modeling, doxorubicin, drug deliveryhttps://www.dovepress.com/blood-nanoparticle-interactions-create-a-brain-delivery-superhighway-f-peer-reviewed-fulltext-article-IJNbbbbrain targetingcnsmodelingdoxorubicindrug delivery |
| spellingShingle | Li Z Kovshova T Malinovskaya J Knoll J Shanehsazzadeh S Osipova N Chernysheva A Melnikov P Gelperina S Wacker MG Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin International Journal of Nanomedicine bbb brain targeting cns modeling doxorubicin drug delivery |
| title | Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin |
| title_full | Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin |
| title_fullStr | Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin |
| title_full_unstemmed | Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin |
| title_short | Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin |
| title_sort | blood nanoparticle interactions create a brain delivery superhighway for doxorubicin |
| topic | bbb brain targeting cns modeling doxorubicin drug delivery |
| url | https://www.dovepress.com/blood-nanoparticle-interactions-create-a-brain-delivery-superhighway-f-peer-reviewed-fulltext-article-IJN |
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