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

07:00 EST 28th December 2018 | BioPortfolio

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

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. Further, 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.


Journal Details

This article was published in the following journal.

Name: Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995


DeepDyve research library

PubMed Articles [17941 Associated PubMed Articles listed on BioPortfolio]

Antithrombotic Agents.

Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless...

Clinical characteristics of exogenous progestogen hypersensitivity.

Autoimmune progesterone dermatitis is a rare disease characterized by eruption recurrence in the luteal phase of each menstrual cycle. As synthetic progesterones are increasingly used for assisted rep...

Design, formulation and evaluation of novel dissolving microarray patches containing a long-acting rilpivirine nanosuspension.

One means of combating the spread of human immunodeficiency virus (HIV) is through the delivery of long-acting, antiretroviral (ARV) drugs for prevention and treatment. The development of a discreet, ...

Progesterone in vitro increases growth, motility and progesterone receptor expression in third stage larvae of Toxocara canis.

The in vitro effect of progesterone in T. canis larvae on their enlargement and motility were evaluated, together to the possible presence of progesterone receptors (PRs). T. canis larvae were culture...

Ex Vivo Evaluation of Intravaginal Progesterone and Testosterone to Treat the Luteal-phase Deficiency and Vaginal Atrophy.

The purpose of this study was to evaluate the transmucosal permeation of progesterone and testosterone using Pentravan as its vehicle for vaginal delivery. Progesterone deficiency is a hormone imbalan...

Clinical Trials [7140 Associated Clinical Trials listed on BioPortfolio]

Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

The purpose of this study is to evaluate the two suggested therapies for prevention of recurrent preterm birth (PTB) in women with a prior spontaneous preterm birth, vaginal and intramuscu...

Role of 200 mg Versus 400mg Vaginal Progesterone in Prevention of Preterm Labor in Twin Gestation

The objective of the present study is to evaluate the effectiveness of two doses of vaginal progesterone(200mg versus400mg) and placebo in improving gestational age in twin pregnancy and i...

17 Alfa Hydroxyprogesterone Caproate Versus Natural Progesterone for the Prevention of Preterm Labor

Preterm deliveries play a significant role in neonatal morbidity and mortality. Previous studies showed that administration of progesterone to pregnant women at high risk, decrease spontan...

Safer Choices 2 - HIV, STD, & Pregnancy Prevention Program

The purpose of the study is to adapt, implement, and evaluate an effective theoretically-based, high school HIV prevention program,Safer Choices, for higher risk youth in alternative schoo...

Vaginal Progesterone for the Prevention of Preterm Birth in Twins

This trial is a randomised, multi-centre, 2 x 2 factorial designed pilot trial with two factors of 200mg vs. 400mg progesterone self-administered daily from 11-14 weeks' gestation vs. 20-2...

Medical and Biotech [MESH] Definitions

A derivative of CHLORAL HYDRATE that was used as a sedative but has been replaced by safer and more effective drugs. Its most common use is as a general anesthetic in animal experiments.

A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.

Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.

The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.

Steroidal compounds related to PROGESTERONE, the major mammalian progestational hormone. Progesterone congeners include important progesterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with progestational activities.

Quick Search


DeepDyve research library

Relevant Topics

Women's Health
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...

Drug Delivery
<!--LGfEGNT2Lhm-->Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals.  <!--LGfEGNT2Lhm-->Drug delivery technologies are <!--LGfEGNT2Lhm-->patent pr...

Obstetrics and gynaecology
Fertility Menopause Obstetrics & Gynaecology Osteoporosis Women's Health Obstetrics and gynaecology comprises the care of the pregnant woman, her unborn child and the management of diseases specific to women. Most consultant...

Searches Linking to this Article