Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption
The management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood–brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused u...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1498 |
| _version_ | 1827604584030273536 |
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| author | Charlotte Bérard Stéphane Desgranges Noé Dumas Anthony Novell Benoit Larrat Mourad Hamimed Nicolas Taulier Marie-Anne Estève Florian Correard Christiane Contino-Pépin |
| author_facet | Charlotte Bérard Stéphane Desgranges Noé Dumas Anthony Novell Benoit Larrat Mourad Hamimed Nicolas Taulier Marie-Anne Estève Florian Correard Christiane Contino-Pépin |
| author_sort | Charlotte Bérard |
| collection | DOAJ |
| description | The management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood–brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused ultrasound-mediated blood–brain barrier disruption using microbubbles is an attractive method to overcome this barrier, showing promising results in clinical trials. Therefore, nanoemulsions combined with this technology represent a real opportunity to bypass the constraints imposed by the blood–brain barrier and improve the treatment of brain diseases. In this work, a stable freeze-dried emulsion of perfluorooctyl bromide nanodroplets stabilized with home-made fluorinated surfactants able to carry hydrophobic agents is developed. This formulation is biocompatible and droplets composing the emulsion are internalized in multiple cell lines. After intravenous administration in mice, droplets are eliminated from the bloodstream in 24 h (blood half-life (t<sub>1/2</sub>) = 3.11 h) and no long-term toxicity is expected since they are completely excreted from mice’ bodies after 72 h. In addition, intracerebral accumulation of tagged droplets is safely and significantly increased after focused ultrasound-mediated blood–brain barrier disruption. Thus, the proposed nanoemulsion appears as a promising nanocarrier for a successful focused ultrasound-mediated brain delivery of hydrophobic agents. |
| first_indexed | 2024-03-09T06:03:12Z |
| format | Article |
| id | doaj.art-47fe15a5d2e34e3db4a06336a18d74b6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T06:03:12Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-47fe15a5d2e34e3db4a06336a18d74b62023-12-03T12:06:28ZengMDPI AGPharmaceutics1999-49232022-07-01147149810.3390/pharmaceutics14071498Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier DisruptionCharlotte Bérard0Stéphane Desgranges1Noé Dumas2Anthony Novell3Benoit Larrat4Mourad Hamimed5Nicolas Taulier6Marie-Anne Estève7Florian Correard8Christiane Contino-Pépin9Aix Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, Hôpital Timone, Service Pharmacie, 13005 Marseille, FranceAvignon Université, Unité Propre de Recherche et d’Innovation, Équipe Systèmes Amphiphiles Bioactifs et Formulations Eco-Compatibles, 84000 Avignon, FranceAix Marseille Univ, CNRS, INP, Inst Neurophysiopathol, 13005 Marseille, FranceUniversité Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, 91401 Orsay, FranceUniversité Paris Saclay, CEA, CNRS, NeuroSpin/BAOBAB, 91191 Gif-sur-Yvette, FranceAix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, SMARTc Unit, COMPO Inria—Inserm Project Team, 13005 Marseille, FranceSorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale—LIB, 75006 Paris, FranceAix Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, Hôpital Timone, Service Pharmacie, 13005 Marseille, FranceAix Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, Hôpital Timone, Service Pharmacie, 13005 Marseille, FranceAvignon Université, Unité Propre de Recherche et d’Innovation, Équipe Systèmes Amphiphiles Bioactifs et Formulations Eco-Compatibles, 84000 Avignon, FranceThe management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood–brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused ultrasound-mediated blood–brain barrier disruption using microbubbles is an attractive method to overcome this barrier, showing promising results in clinical trials. Therefore, nanoemulsions combined with this technology represent a real opportunity to bypass the constraints imposed by the blood–brain barrier and improve the treatment of brain diseases. In this work, a stable freeze-dried emulsion of perfluorooctyl bromide nanodroplets stabilized with home-made fluorinated surfactants able to carry hydrophobic agents is developed. This formulation is biocompatible and droplets composing the emulsion are internalized in multiple cell lines. After intravenous administration in mice, droplets are eliminated from the bloodstream in 24 h (blood half-life (t<sub>1/2</sub>) = 3.11 h) and no long-term toxicity is expected since they are completely excreted from mice’ bodies after 72 h. In addition, intracerebral accumulation of tagged droplets is safely and significantly increased after focused ultrasound-mediated blood–brain barrier disruption. Thus, the proposed nanoemulsion appears as a promising nanocarrier for a successful focused ultrasound-mediated brain delivery of hydrophobic agents.https://www.mdpi.com/1999-4923/14/7/1498nanoemulsionsdropletsbrain diseasesblood–brain barrierultrasounddrug carrier |
| spellingShingle | Charlotte Bérard Stéphane Desgranges Noé Dumas Anthony Novell Benoit Larrat Mourad Hamimed Nicolas Taulier Marie-Anne Estève Florian Correard Christiane Contino-Pépin Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption Pharmaceutics nanoemulsions droplets brain diseases blood–brain barrier ultrasound drug carrier |
| title | Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption |
| title_full | Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption |
| title_fullStr | Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption |
| title_full_unstemmed | Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption |
| title_short | Perfluorocarbon Nanodroplets as Potential Nanocarriers for Brain Delivery Assisted by Focused Ultrasound-Mediated Blood–Brain Barrier Disruption |
| title_sort | perfluorocarbon nanodroplets as potential nanocarriers for brain delivery assisted by focused ultrasound mediated blood brain barrier disruption |
| topic | nanoemulsions droplets brain diseases blood–brain barrier ultrasound drug carrier |
| url | https://www.mdpi.com/1999-4923/14/7/1498 |
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