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Uptake of dendrimer-drug by different cell types in the hippocampus after hypoxic-ischemic insult in neonatal mice: Effects of injury, microglial activation and hypothermia.
Nemeth, Christina L; Drummond, Gabrielle T; Mishra, Manoj K; Zhang, Fan; Carr, Patrice; Garcia, Maxine S; Doman, Sydney; Fatemi, Ali; Johnston, Michael V; Kannan, Rangaramanujam M; Kannan, Sujatha; Wilson, Mary Ann.
Afiliación
  • Nemeth CL; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD 21287, USA.
  • Drummond GT; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA.
  • Mishra MK; Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA.
  • Zhang F; Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA.
  • Carr P; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA.
  • Garcia MS; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA.
  • Doman S; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA.
  • Fatemi A; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD 21287, USA.
  • Johnston MV; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD 21287, USA.
  • Kannan RM; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA.
  • Kannan S; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, The Charlotte R. Bloomberg Children's Center, 1800 Orleans Street, Suite 6318D, Baltimore, MD 21287, USA. Electro
  • Wilson MA; Hugo W. Moser Research Institute at Kennedy Krieger, 707 N Broadway, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD 21287, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 N. Wol
Nanomedicine ; 13(7): 2359-2369, 2017 Oct.
Article en En | MEDLINE | ID: mdl-28669854
ABSTRACT
Perinatal hypoxic-ischemic encephalopathy (HIE) can result in neurodevelopmental disability, including cerebral palsy. The only treatment, hypothermia, provides incomplete neuroprotection. Hydroxyl polyamidoamine (PAMAM) dendrimers are being explored for targeted delivery of therapy for HIE. Understanding the biodistribution of dendrimer-conjugated drugs into microglia, neurons and astrocytes after brain injury is essential for optimizing drug delivery. We conjugated N-acetyl-L-cysteine to Cy5-labeled PAMAM dendrimer (Cy5-D-NAC) and used a mouse model of perinatal HIE to study effects of timing of administration, hypothermia, brain injury, and microglial activation on uptake. Dendrimer conjugation delivered therapy most effectively to activated microglia but also targeted some astrocytes and injured neurons. Cy5-D-NAC uptake was correlated with brain injury in all cell types and with activated morphology in microglia. Uptake was not inhibited by hypothermia, except in CD68+ microglia. Thus, dendrimer-conjugated drug delivery can target microglia, astrocytes and neurons and can be used in combination with hypothermia for treatment of HIE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcisteína / Portadores de Fármacos / Sistemas de Liberación de Medicamentos / Hipoxia-Isquemia Encefálica / Dendrímeros / Antioxidantes Límite: Animals Idioma: En Revista: Nanomedicine Asunto de la revista: BIOTECNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcisteína / Portadores de Fármacos / Sistemas de Liberación de Medicamentos / Hipoxia-Isquemia Encefálica / Dendrímeros / Antioxidantes Límite: Animals Idioma: En Revista: Nanomedicine Asunto de la revista: BIOTECNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos