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Methamphetamine enhances caveolar transport of therapeutic agents across the rodent blood-brain barrier.
Chang, Jui-Hsien; Greene, Chris; Frudd, Karen; Araujo Dos Santos, Leonardo; Futter, Clare; Nichols, Benjamin J; Campbell, Matthew; Turowski, Patric.
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  • Chang JH; UCL Institute of Ophthalmology, University College London, London, UK.
  • Greene C; Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
  • Frudd K; UCL Institute of Ophthalmology, University College London, London, UK.
  • Araujo Dos Santos L; UCL Institute of Ophthalmology, University College London, London, UK.
  • Futter C; UCL Institute of Ophthalmology, University College London, London, UK.
  • Nichols BJ; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Campbell M; Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
  • Turowski P; UCL Institute of Ophthalmology, University College London, London, UK.
Cell Rep Med ; 3(1): 100497, 2022 01 18.
Article en En | MEDLINE | ID: mdl-35106509
The blood-brain barrier (BBB) restricts clinically relevant accumulation of many therapeutics in the CNS. Low-dose methamphetamine (METH) induces fluid-phase transcytosis across BBB endothelial cells in vitro and could be used to enhance CNS drug delivery. Here, we show that low-dose METH induces significant BBB leakage in rodents ex vivo and in vivo. Notably, METH leaves tight junctions intact and induces transient leakage via caveolar transport, which is suppressed at 4°C and in caveolin-1 (CAV1) knockout mice. METH enhances brain penetration of both small therapeutic molecules, such as doxorubicin (DOX), and large proteins. Lastly, METH improves the therapeutic efficacy of DOX in a mouse model of glioblastoma, as measured by a 25% increase in median survival time and a significant reduction in satellite lesions. Collectively, our data indicate that caveolar transport at the adult BBB is agonist inducible and that METH can enhance drug delivery to the CNS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Barrera Hematoencefálica / Caveolas / Metanfetamina Límite: Animals Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Barrera Hematoencefálica / Caveolas / Metanfetamina Límite: Animals Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos