Dual-responsive ionic liquid based foam-to-gel for precision vaginal delivery of progesterone

Area of Science:

• Pharmaceutics
• Biomaterials Science
• Reproductive Medicine

Background:

• Vaginal progesterone is preferred for luteal phase support in assisted reproductive technology (ART) due to the uterine first-pass effect.
• Current formulations face limitations in drug solubility and vaginal mucosal penetration, impacting therapeutic efficacy.
• Developing advanced delivery systems is crucial for optimizing progesterone's role in infertility treatment.

Purpose of the Study:

• To develop and characterize an ionic liquid-based foam-to-gel system (IL-FOAM) for enhanced vaginal delivery of progesterone.
• To evaluate the solubility, stability, mucoadhesion, and transmucosal penetration of the IL-FOAM.
• To assess the in vivo uterine targeting efficiency and safety profile of the novel formulation.

Main Methods:

• Formulation of IL-FOAM using choline oleate, propellants, and Poloxamer 407 (P407) for dual-responsive gelation.
• Assessment of progesterone solubility enhancement and foam characteristics (expansion, ejection, gelation).
• Evaluation using 3D-printed vaginal models, ex vivo mucosal penetration studies, and in vivo pharmacokinetic/safety studies in Sprague-Dawley rats.

Main Results:

• Choline oleate significantly increased progesterone solubility by over 1000-fold.
• IL-FOAM demonstrated rapid foam-to-gel transition under physiological conditions, achieving complete vaginal coverage and 24-hour gel retention.
• Ex vivo studies showed a 3-fold higher mucosal penetration ratio compared to Crinone®, and in vivo studies revealed superior uterine targeting efficiency (85.96%) with a favorable safety profile.

Conclusions:

• The dual-responsive IL-FOAM is a promising strategy for vaginal progesterone delivery, overcoming limitations of current formulations.
• This system offers enhanced drug solubility, prolonged retention, and improved uterine targeting, potentially advancing luteal phase support in ART.
• The IL-FOAM formulation provides a novel approach for sustained and effective progesterone delivery in infertility treatment.