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Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth.
Zierden, Hannah C; Ortiz, Jairo I; DeLong, Kevin; Yu, Jingqi; Li, Gaoshan; Dimitrion, Peter; Bensouda, Sabrine; Laney, Victoria; Bailey, Anna; Anders, Nicole M; Scardina, Morgan; Mahendroo, Mala; Mesiano, Sam; Burd, Irina; Wagner, Gunter; Hanes, Justin; Ensign, Laura M.
  • Zierden HC; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Ortiz JI; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • DeLong K; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Yu J; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Li G; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Dimitrion P; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Bensouda S; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Laney V; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Bailey A; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Anders NM; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Scardina M; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Mahendroo M; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Mesiano S; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Burd I; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wagner G; Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Hanes J; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Ensign LM; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Sci Transl Med ; 13(576)2021 01 13.
Article en En | MEDLINE | ID: mdl-33441428
ABSTRACT
Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone caproate (Makena) nor vaginal progesterone gel (Crinone) was sufficient to prevent inflammation-induced PTB, consistent with recent clinical trial failures. However, we found that vaginal delivery of mucoinert nanosuspensions of histone deacetylase (HDAC) inhibitors, in some cases with the addition of progesterone, prevented PTB and resulted in delivery of live pups exhibiting neurotypical development. In human myometrial cells in vitro, the P4/HDAC inhibitor combination both inhibited cell contractility and promoted the anti-inflammatory action of P4 by increasing progesterone receptor B stability. Here, we demonstrate the use of vaginally delivered drugs to prevent intrauterine inflammation-induced PTB resulting in the birth of live offspring in a preclinical animal model.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Nacimiento Prematuro Límite: Animals / Pregnancy Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
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PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Nacimiento Prematuro Límite: Animals / Pregnancy Idioma: En Año: 2021 Tipo del documento: Article