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Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation.
Schneider, Craig S; Xu, Qingguo; Boylan, Nicholas J; Chisholm, Jane; Tang, Benjamin C; Schuster, Benjamin S; Henning, Andreas; Ensign, Laura M; Lee, Ethan; Adstamongkonkul, Pichet; Simons, Brian W; Wang, Sho-Yu S; Gong, Xiaoqun; Yu, Tao; Boyle, Michael P; Suk, Jung Soo; Hanes, Justin.
Afiliação
  • Schneider CS; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Xu Q; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Boylan NJ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Chisholm J; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Tang BC; Wilmer Eye Institute, Johns Hopkins Medical Institute, Baltimore, MD 21287, USA.
  • Schuster BS; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Henning A; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Ensign LM; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Lee E; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Adstamongkonkul P; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Simons BW; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wang SS; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Gong X; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Yu T; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Boyle MP; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Suk JS; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Hanes J; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Sci Adv ; 3(4): e1601556, 2017 Apr.
Article em En | MEDLINE | ID: mdl-28435870
Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP. We compared in vivo behaviors of variously sized, polystyrene-based MAP and MPP in the lungs following inhalation. MAP, regardless of particle size, were aggregated and poorly distributed throughout the airways, leading to rapid clearance from the lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and markedly enhanced retention compared to size-matched MAP. On the basis of these findings, we formulated biodegradable MPP (b-MPP) with an average diameter of <300 nm and examined their behavior following inhalation relative to similarly sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo correlated to a more uniform distribution within the airways and enhanced lung retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse model of acute lung inflammation compared to both carrier-free DP and DP-loaded MAP. These studies provide a careful head-to-head comparison of MAP versus MPP following inhalation and challenge a long-standing dogma that favored the use of MAP for pulmonary drug delivery.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia / Dexametasona / Sistemas de Liberação de Medicamentos / Mucosa Respiratória / Nanopartículas / Plásticos Biodegradáveis Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia / Dexametasona / Sistemas de Liberação de Medicamentos / Mucosa Respiratória / Nanopartículas / Plásticos Biodegradáveis Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article