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      Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth

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          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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          A simple practice guide for dose conversion between animals and human

          Anroop B. Nair, Shery Jacob (2016)
          Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
          Article 0 comments Cited 1238 times – based on 0 reviews     Review now
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            Born Too Soon: The global epidemiology of 15 million preterm births

            Hannah Blencowe, Simon Cousens, Doris Chou … (2013)
            This second paper in the Born Too Soon supplement presents a review of the epidemiology of preterm birth, and its burden globally, including priorities for action to improve the data. Worldwide an estimated 11.1% of all livebirths in 2010 were born preterm (14.9 million babies born before 37 weeks of gestation), with preterm birth rates increasing in most countries with reliable trend data. Direct complications of preterm birth account for one million deaths each year, and preterm birth is a risk factor in over 50% of all neonatal deaths. In addition, preterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care. The economic costs of preterm birth are large in terms of immediate neonatal intensive care, ongoing long-term complex health needs, as well as lost economic productivity. Preterm birth is a syndrome with a variety of causes and underlying factors usually divided into spontaneous and provider-initiated preterm births. Consistent recording of all pregnancy outcomes, including stillbirths, and standard application of preterm definitions is important in all settings to advance both the understanding and the monitoring of trends. Context specific innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. Strengthened data systems are required to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.
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              The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review.

              Laetitia Prut, Catherine Belzung (2003)
              The open field is a very popular animal model of anxiety-like behavior. An overview of the literature on the action elicited by effective or putative anxiolytics in animal subjected to this procedure indicates that classical treatments such as benzodiazepine receptor full agonists or 5-HT(1A) receptor full or partial agonists elicit an anxiolytic-like effect in this procedure in most cases (approximately 2/3). However, compounds (triazolobenzodiazepines such as adinazolam and alprazolam, selective serotonin reuptake inhibitors) that have a different spectrum of therapeutic efficacy in anxiety disorders such as panic attacks, generalized anxiety disorder or obsessive-compulsive disorder were poorly effective as anxiolytics in the open field test, suggesting that this paradigm may not model features of anxiety disorders. The procedure is also relevant for the study of compounds endowed with anxiogenic effects, as such effects were detected after treatments with benzodiazepine receptor inverse agonists or with corticotropin releasing factor (CRF) receptor agonists.
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                Author and article information

                Contributors
                Journal
                Title: Science Translational Medicine
                Abbreviated Title: Sci. Transl. Med.
                Publisher: American Association for the Advancement of Science (AAAS)
                ISSN (Print): 1946-6234
                ISSN (Electronic): 1946-6242
                Publication date Created: January 13 2021
                Publication date Created: January 13 2021
                Publication date (Electronic): January 13 2021
                Publication date (Print): January 13 2021
                Volume: 13
                Issue: 576
                Page: eabc6245
                Affiliations
                [1 ]Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
                [2 ]Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
                [3 ]Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
                [4 ]Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
                [5 ]Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
                [6 ]Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
                [7 ]Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
                [8 ]Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21287, USA.
                [9 ]Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520, USA.
                Article
                DOI: 10.1126/scitranslmed.abc6245
                SO-VID: 7a2e4963-f5b4-4e85-89b6-da1507f215f4
                Copyright © © 2021
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                https://www.sciencemag.org/about/science-licenses-journal-article-reuse

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