Evidence map›Paper›PMID 30597245›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2019

Development of a mucoinert progesterone nanosuspension for safer and more effective prevention of preterm birth.

Thuy Hoang, Hannah Zierden, Abhijit Date, Jairo Ortiz, Sanjeev Gumber, Nicole Anders, Ping He, James Segars, Justin Hanes, Mala Mahendroo and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Nanomedicine for Maternal and Fetal Health.Small (Weinheim an der Bergstrasse, Germany) · 2024
    Review
  9. Hypotonic, gel-forming delivery system for vaginal drug administration.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Next generation strategies for preventing preterm birth.Advanced drug delivery reviews · 2021
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Thuy HoangThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hannah ZierdenThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Abhijit DateThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jairo OrtizThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sanjeev GumberDivision of Pathology, Yerkes National Primate Research Center, Atlanta, GA 30322, USA.
Nicole AndersThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA.
Ping HeThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA.
James SegarsDepartment of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA.
Justin HanesThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA.
Mala MahendrooDepartment of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Laura M EnsignThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA; Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, Baltimore, MD 21287, USA. Electronic address: lensign@jhmi.edu.
Johns Hopkins University · USEmory National Primate Research CenterThe University of Texas Southwestern Medical Center · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
TRPA1 Physiology in Diabetes, Metabolic Syndrome, and MetabolismP20GM113134 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI Michael A. Ortega · 2017 to 2026
$21.5M
NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR003098NEI NIH HHS P30 EY001765NIGMS NIH HHS P20 GM113134NIH HHS P51 OD011132
6 · The paper itself

Abstract

Preterm birth (PTB) is a significant global problem, but few therapeutic options exist. Vaginal progesterone supplementation has been demonstrated to reduce PTB rates in women with a sonographic short cervix, yet there has been little investigation into the most effective dose or delivery form. Further, vaginal products like progesterone gel often contain excipients that cause local toxicity, irritation, and leakage. Here, we describe the development and characterization of a mucoinert vaginal progesterone nanosuspension formulation for improved drug delivery to the female reproductive tract. We compare the pharmacokinetics and pharmacodynamics to the clinical comparator progesterone gel in pregnant mice and demonstrate increased vaginal absorption and biodistribution via the uterine first-pass effect. Importantly, the unique plasma progesterone double peak observed in humans, reflecting recirculation from the uterus, was also observed in pregnant mice with vaginal dosing. We adapted a mouse model of progesterone withdrawal that was previously believed to be incompatible with testing the efficacy of exogenous progestins, and are first to demonstrate efficacy in preventing preterm birth with vaginal progesterone in this model. Further, improved vaginal progesterone delivery by the nanosuspension led to increased efficacy in PTB prevention. Additionally, we identified histological and transcriptional evidence of cervical and uterine toxicity with a single vaginal administration of the clinical gel that are absent after dosing with the mucoinert nanosuspension formulation. We demonstrate that a progesterone formulation that is designed for improved vaginal progesterone absorption and vaginal biocompatibility could be more effective for PTB prevention.

Indexed as

Administration, IntravaginalAnimalsAnimals, NewbornFemaleHumansMiceNanogelsPharmaceutical VehiclesPregnancyPremature BirthProgesteroneProgestinsTissue DistributionVaginal Creams, Foams, and JelliesNanogelsPharmaceutical VehiclesProgesteroneProgestinsVaginal Creams, Foams, and JelliesCrinoneNanomedicineNanotechnologyUterine first-pass effectVaginal

Identifiers

PMID30597245
PMCPMC6398330
OpenAlexW2907497194

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.