Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies
Nanoengineered encapsulation presents a promising strategy for targeted drug delivery to specific regions in the body. While polyelectrolyte-based biodegradable microcapsules can achieve highly localised drug release in tissues and cell cultures, delivering drugs to intracellular sites in the brain...
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Elsevier
2025-04-01
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| author | Olga Kopach Olga A. Sindeeva Kaiyu Zheng Eleanor McGowan Gleb B. Sukhorukov Dmitri A. Rusakov |
| author_facet | Olga Kopach Olga A. Sindeeva Kaiyu Zheng Eleanor McGowan Gleb B. Sukhorukov Dmitri A. Rusakov |
| author_sort | Olga Kopach |
| collection | DOAJ |
| description | Nanoengineered encapsulation presents a promising strategy for targeted drug delivery to specific regions in the body. While polyelectrolyte-based biodegradable microcapsules can achieve highly localised drug release in tissues and cell cultures, delivering drugs to intracellular sites in the brain remains a significant challenge. In this study, we utilized advanced imaging techniques, both in vitro and in vivo, to investigate whether brain neurons can internalise polyelectrolyte-based microcapsules designed for drug delivery. High-resolution live-cell imaging revealed that differentiating N2A cells actively internalise microcapsules, often incorporating multiple capsules per cell. Likewise, primary hippocampal and cortical neurons were observed to effectively internalise polymeric microcapsules. In the intact brain, multiplexed two-photon excitation imaging in vivo confirmed the internalisation of microcapsules by cortical neurons following delivery to the somatosensory brain region. This internalisation was time-dependent, correlated with particle size and mediated by a macropinocytosis mechanism that appears to bypass lysosomal formation. Importantly, the presence of internalised microcapsules did not impair neuronal function, as neurons maintained normal firing activity and action potential characteristics. Furthermore, no adverse effects were observed after a week of microcapsule presence in the mouse brain. Our findings indicate that polymeric microcapsules are effective and safe carriers for intracellular drug delivery to brain neurons, providing a targeted approach with potential therapeutic applications. |
| format | Article |
| id | doaj-art-d8286361e967438386ee6cb63f58863e |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-d8286361e967438386ee6cb63f58863e2025-01-30T05:14:49ZengElsevierMaterials Today Bio2590-00642025-04-0131101493Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studiesOlga Kopach0Olga A. Sindeeva1Kaiyu Zheng2Eleanor McGowan3Gleb B. Sukhorukov4Dmitri A. Rusakov5Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; Neuroscience and Cell Biology Research Institute, City St George's University of London, Cranmer Terrace, London SW17 0RE, UK; Corresponding author. Neuroscience and Cell Biology Research Institute, City St George's University of London, Cranmer Terrace, London SW17 0RE, UK.School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UKDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UKDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UKSchool of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UKDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; Corresponding author.Nanoengineered encapsulation presents a promising strategy for targeted drug delivery to specific regions in the body. While polyelectrolyte-based biodegradable microcapsules can achieve highly localised drug release in tissues and cell cultures, delivering drugs to intracellular sites in the brain remains a significant challenge. In this study, we utilized advanced imaging techniques, both in vitro and in vivo, to investigate whether brain neurons can internalise polyelectrolyte-based microcapsules designed for drug delivery. High-resolution live-cell imaging revealed that differentiating N2A cells actively internalise microcapsules, often incorporating multiple capsules per cell. Likewise, primary hippocampal and cortical neurons were observed to effectively internalise polymeric microcapsules. In the intact brain, multiplexed two-photon excitation imaging in vivo confirmed the internalisation of microcapsules by cortical neurons following delivery to the somatosensory brain region. This internalisation was time-dependent, correlated with particle size and mediated by a macropinocytosis mechanism that appears to bypass lysosomal formation. Importantly, the presence of internalised microcapsules did not impair neuronal function, as neurons maintained normal firing activity and action potential characteristics. Furthermore, no adverse effects were observed after a week of microcapsule presence in the mouse brain. Our findings indicate that polymeric microcapsules are effective and safe carriers for intracellular drug delivery to brain neurons, providing a targeted approach with potential therapeutic applications.http://www.sciencedirect.com/science/article/pii/S2590006425000511Polyelectrolyte microcapsulesBrain neuronsInternalisationIntracellular deliveryBrain targeting |
| spellingShingle | Olga Kopach Olga A. Sindeeva Kaiyu Zheng Eleanor McGowan Gleb B. Sukhorukov Dmitri A. Rusakov Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies Materials Today Bio Polyelectrolyte microcapsules Brain neurons Internalisation Intracellular delivery Brain targeting |
| title | Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies |
| title_full | Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies |
| title_fullStr | Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies |
| title_full_unstemmed | Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies |
| title_short | Brain neurons internalise polymeric micron-sized capsules: Insights from in vitro and in vivo studies |
| title_sort | brain neurons internalise polymeric micron sized capsules insights from in vitro and in vivo studies |
| topic | Polyelectrolyte microcapsules Brain neurons Internalisation Intracellular delivery Brain targeting |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000511 |
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