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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2021; 81(07): 789-806
DOI: 10.1055/a-1369-9395
GebFra Science
Review

Development of Hormonal Intravaginal Rings: Technology and Challenges

Die Entwicklung hormonhaltiger Vaginalringe: Technologie und Herausforderungen
Fojan Rafiei
1   Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
,
Hadi Tabesh
1   Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
,
Shayan Farzad
2   Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States
,
Farah Farzaneh
3   Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Maryam Rezaei
1   Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
,
Fateme Hosseinzade
1   Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
,
Khosrow Mottaghy
4   Institute of Physiology, RWTH Aachen University, Aachen, Germany
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Abstract

Intravaginal rings (IVRs) are minimally invasive polymeric devices specifically designed to be used for the sustained and prolonged release of various type of drugs such as hormones. One of the benefits of using topical drug delivery systems (e.g., IVRs) is the fact that systemic drug delivery may cause drug resistance due to elevated drug levels. Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects. In addition, when a drug is administered vaginally, the hepatic first-pass effect is avoided, resulting in higher absorption. Contraception and treatments for specific diseases such as endometriosis and hormone deficiencies can be improved by the administration of hormones via an IVR. This article aims to classify and compare various designs of commercially available and non-commercial hormonal IVRs and to analyze their performance. Current challenges affecting the development of IVRs are investigated, and proposed solutions are discussed. A comprehensive search of publications in MEDLINE/PubMed and of commercial product data of IVRs was performed, and the materials, designs, performance, and applications (e.g., contraception, endometriosis, estrogen deficiency and urogenital atrophy) of hormonal IVRs were thoroughly evaluated. Most hormonal IVRs administer female sex hormones, i.e., estrogen and progestogens. In terms of material, IVRs are divided into 3 main groups: silicone, polyurethane, and polyethylene-co-vinyl acetate IVRs. As regards their design, there are 4 major designs for IVRs which strongly affect their performance and the timing and rate of hormone release. Important challenges include reducing the burst release and maintaining the bioavailability of hormones at their site of action over a prolonged period of administration as well as lowering production costs. Hormonal IVRs are a promising method which could be used to facilitate combination therapies by administering multiple drugs in a single IVR while eliminating the side effects of conventional drug administration methods. IVRs could considerably improve womenʼs quality of life all over the world within a short period of time.

Zusammenfassung

Vaginalringe (IVRs) sind minimalinvasive polymere Vorrichtungen, die speziell für die langfristige und anhaltende Gabe von spezifischen Medikamenten wie Hormonen entwickelt wurden. Der Vorteil eines örtlichen Wirkstoffabgabesystems (z. B. eines IVR) liegt darin, dass die systemische Wirkstoffabgabe wegen des erhöhten Medikamentenspiegels zu einer Medikamentenresistenz führen kann. Hinzu kommt noch, dass eine örtliche Gabe von Medikamenten zu einer höheren Medikamentenkonzentration im Zielgewebe führt und mit geringeren Nebenwirkungen behaftet ist. Außerdem wird durch die intravaginale Gabe von Medikamenten der First-Pass-Effekt vermieden, was zu einer höheren Medikamentenaufnahme führt. Verhütungsmethoden und Behandlungen von bestimmten Erkrankungen wie Endometriose und Hormondefizite profitieren von dem Einsatz hormoneller IVRs. Ziel dieser Studie war es, verschiedene kommerzielle und nicht kommerzielle hormonelle IVR-Modelle zu klassifizieren, zu vergleichen und ihre Leistungen zu analysieren. Es wurden auch die aktuellen Herausforderungen bei der Entwicklung von IVR-Modelle untersucht und grundlegende Lösungsvorschläge ausführlich besprochen. Zunächst wurde eine umfassende Recherche in MEDLINE/PubMed durchgeführt und die Daten kommerzieller IVR-Produkte wurden gesichtet, um danach die Materialien, Modelle, Leistungen und Anwendungsgebiete (z. B. Verhütung, Endometriose, Östogenmangel und urogenitale Atrophie) von hormonellen IVRs eingehend zu untersuchen. Die meisten hormonellen IVRs werden zur Verabreichung von weiblichen Sexualhormonen, d. h. Östrogenen und Gestagenen, eingesetzt. IVRs können anhand ihrer Grundmaterialien in 3 Hauptgruppen unterteilt werden: Es gibt IVRs aus Silikon, aus Polyurethan und aus Ethylen-Vinylacetat-Copolymere. Was die Ausformung angeht, gibt es im Wesentlichen 4 IVR-Modelle, wobei die jeweilige Form sich stark auf die Leistung sowie den Zeitpunkt und die Geschwindigkeit der Hormonfreisetzung auswirkt. Die wichtigsten Herausforderungen bestehen darin, einen plötzlichen Wirkstoffschub zu verhindern, die Bioverfügbarkeit der Hormone im Zielgebiet über einen längeren Zeitraum aufrechtzuhalten und die Herstellkosten zu senken. Hormonelle IVRs versprechen, aktuelle Herausforderungen mithilfe innovativer Entwicklungen zu bewältigen, indem sie den zielgenauen Transport biomedizinischer Wirkstoffe an den Wirkort und dadurch eine Kombinationstherapie aus mehreren Medikamenten in einem einzigen IVR ermöglichen, ohne die Nebenwirkungen von konventionellen Methoden der Medikamentengabe. Auf längere Sicht könnten IVRs innerhalb kurzer Zeit zu einer erheblichen Verbesserung der Lebensqualität von Frauen weltweit beitragen.

Key words

intravaginal ring - hormones - contraception - endometriosis - estrogen deficiency - urogenital atrophy

Schlüsselwörter

Intravaginalring - Hormone - Verhütung - Endometriose - Östrogenmangel - urogenitale Atrophie


Publication History

Received: 08 November 2020

Accepted after revision: 20 January 2021

Article published online:
13 July 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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