Multiple hour antifibrotic drug release enabled by a thermosensitive quadpolymer.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems
• Gynecological Therapeutics

Background:

• Injectable therapies for uterine fibroids are challenging due to tumor structure and location.
• Existing treatments may not preserve fertility, highlighting the need for innovative solutions.
• Localized drug delivery offers a targeted approach to managing uterine fibroids.

Purpose of the Study:

• To develop a thermosensitive injectable quadpolymer for sustained anti-fibrotic drug release.
• To evaluate the quadpolymer's efficacy in delivering pirfenidone for uterine fibroid therapy.
• To assess the potential of this system for fertility-preserving treatment options.

Main Methods:

• Synthesized quadpolymers (Poly(NIPAM-co-HEMA-PLA-co-AAc-co-HPG-MA)) via free radical polymerization.
• Optimized sol-gel transition temperature and mechanical stiffness by adjusting monomer ratios.
• Loaded quadpolymer formulations with pirfenidone (hydrophobic drug) and evaluated in vitro drug release and cell proliferation inhibition.

Main Results:

• Quadpolymer 83-7-1-9 (17% w/v) formed a syringeable solution at room temperature and a stable gel at body temperature.
• The gel exhibited partial biodegradation over time.
• Pirfenidone-loaded quadpolymer demonstrated sustained release and preserved drug activity, inhibiting cultured fibroid cell proliferation.

Conclusions:

• Quadpolymer 83-7-1-9 is a promising injectable hydrogel for localized uterine fibroid therapy.
• The system enables sustained release of anti-fibrotic drugs like pirfenidone.
• This approach supports further development for fertility-preserving uterine fibroid treatment.