Formulation-Based Repurposing of Mifepristone Using a Drug-Eluting Intrauterine Insert for Localized Uterine Fibroid Therapy: A Preclinical Study
摘要
The majority of currently available treatments for uterine fibroids (UFs) are invasive and are delivered via either oral or parenteral means. Mifepristone (MFP), a particular drug that alters the activity of progesterone receptors, is selected as the preferred treatment. Presently, it is used for the purpose of inducing abortion. Recent clinical trials have demonstrated that MFP effectively reduces the size of UFs. This study proposes the use of MFP for repurposing UF. The objective of this study was to develop a drug-eluting intrauterine insert (DE-IUI) containing MFP and investigate its effectiveness in targeting the uterus via the intrauterine route. A biodegradable insert with a capsule-like shape was developed using the melting process. The drug exhibited a release rate of 45–50% within a 15-day period, achieving the desired level of degradation. The preclinical in vivo findings demonstrated that the biodegradation of DE-IUI resulted in a substantial decrease in the size of the UF. The MFP-insert was effectively developed and assessed for repurposing to treat UF by targeting the uterus through the vaginal route. Targeted drug delivery to the site of action allows for a decrease in dose, maintaining the desired therapeutic effect and mitigating the side effects associated with current treatments.
Graphical Abstract