Recent advancements and future applications of intrauterine drug delivery systems

ABSTRACT Introduction Intrauterine devices (IUDs) are drug-device combination products that are placed inside the uterus above the endometrium. IUDs contain a therapeutic agent used for contraception and have been shown to have other therapeutic benefits. Over the past century, intrauterine drug delivery systems (IUDDS) have revolutionized women’s health, and they hold immense growth potential in the future for new developments in the therapeutic areas beyond contraception. Areas covered The aim of this review is to offer a comprehensive description of the history, development, and current state of IUDDS, next-generation IUDDS, and future applications of IUDDS in therapeutic areas beyond contraception such as multi-purpose prevention technologies, hormone replacement therapy, endometriosis, uterine fibroids, and endometrial cancer. Expert opinion The uterus’s unique features make it an ideal site for controlled, prolonged, and localized delivery of drugs, ensuring maximum concentration at the target site. Currently, IUDs are the most widely used contraceptive method. Future IUDDS hold the potential to deliver therapeutic agents for broader therapeutic areas for women’s health, potentially aiding in the treatment of various diseases and disorders of the female reproductive system. Further research in development, characterization, and translation is warranted to ensure IUDDS reach their potential in many areas of women’s health. Article highlights The anatomy and physiology of the uterus in relation to intrauterine drug delivery are discussed in the manuscript. The unique features of the uterus, such as the innermost hormonally responsive endometrium layer with rich vasculature, facilitate localized drug absorption, ensuring high localized concentrations of therapeutic agents delivered to the uterine cavity, while minimizing systemic exposure. IUDDS have evolved tremendously in a last century from early designs such as silkworm gut IUDs to modern copper and hormonal IUDs offering long-acting reversible contraception with enhanced safety and efficacy profiles. As a result, IUDDS have gained popularity globally. Currently, one copper IUD and four hormonal IUDs are commercially available in the United States. However, till now there are no generic alternatives. The current research landscape involves investigation of different sizes, shapes, and dose levels of IUDs, the use of alternative materials, as well as additional therapeutic indications. Next-generation IUDs, such as flexible Cu-IUDs, frameless LNG-IUSs, novel T-shaped LNG-IUSs, flexible low-dose Cu-IUDs, and intrauterine balls are in development with the goal to further improve safety, efficacy and patient compliance. A detailed review on the future applications of intrauterine drug delivery systems in the fields of contraception, sexually transmitted infections, gynecological disorders, malignancies, and hormone replacement therapy in various female reproductive disorders is provided. Abbreviations | AIDS | = | Acquired immune deficiency syndrome | | ARV | = | Antiretroviral | | BC | = | Breast cancer | | Cu-IUDs | = | Copper containing intrauterine devices | | EC | = | Endometrial cancer | | EIN | = | Endometrial intraepithelial neoplasia | | ERT | = | Estrogen replacement therapy | | FDA | = | Food and drug administration | | FSH | = | Follicle stimulating hormone | | GnRH | = | Gonadotropin releasing hormone | | Hb | = | Hemoglobin | | HIV | = | Human immunodeficiency virus | | HRT | = | Hormone replacement therapy | | IUD | = | Intrauterine device | | IUDDS | = | Intrauterine drug delivery systems | | IVIVC | = | In vitro in vivo correlation | | LARCs | = | Long-acting reversible contraceptives | | LH | = | Luteinizing hormone | | LNG-IUS | = | Levonorgestrel intrauterine system | | MPTs | = | Multi-purpose prevention technologies | | PDMS | = | Polydimethylsiloxane | | PE | = | Polyethylene | | PR | = | Progesterone receptor | | PR+ | = | Progesterone receptor-positive | | PrEP | = | Pre-exposure prophylaxis | | STIs | = | Sexually transmitted infections | | Zn-IUDs | = | Zinc-based intrauterine devices | Declarations of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Reviewer disclosure Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.