Thermosensitive progesterone hydrogel: a safe and effective new formulation for vaginal application

Area of Science:

• Reproductive Medicine
• Polymer Science
• Drug Delivery Systems

Background:

• Vaginal progesterone delivery is crucial but faces challenges in safety and functionality.
• Existing formulations may not meet clinical needs for effective progesterone (P4) administration.
• Thermosensitive mucoadhesive polymers offer potential for improved vaginal drug delivery.

Purpose of the Study:

• To develop and characterize a novel progesterone (P4) gel formulation for vaginal application.
• To utilize a thermosensitive mucoadhesive polymer, glycol chitin (GC), for enhanced P4 delivery.
• To evaluate the safety and efficacy of the new GC-P4 vaginal gel.

Main Methods:

• Rheological analysis assessed thermogelling, mucoadhesive, mechanical, and viscoelastic properties of GC and GC-P4.
• In vitro studies evaluated P4 release kinetics in vaginal fluid simulant (VFS) and bioactivity using a PR-reporter gene assay.
• In vitro and in vivo safety assessments were conducted on vaginal epithelial cells, Lactobacillus Crispatus, and mouse models.

Main Results:

• The 5% GC-P4 formulation formed a stable, thermosensitive, mucoadhesive hydrogel at 37°C.
• GC-P4 demonstrated controlled P4 release (50% in 4h) and showed no significant cytotoxicity in vitro or in vivo.
• The GC-P4 gel effectively prevented the progression of simple endometrial hyperplasia to complex atypical endometrial hyperplasia in vivo.

Conclusions:

• The developed GC-P4 formulation exhibits favorable characteristics for an effective vaginal progesterone delivery system.
• GC-P4 represents a promising alternative to existing vaginal progesterone formulations.
• This novel formulation addresses the unmet clinical need for safe and functional vaginal P4 delivery.