Single subconjunctival injection formulation with a 5-fluorouracil-poly(lactic) acid controlled-release system for...

Area of Science:

• Ophthalmology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Glaucoma filtration surgery aims to reduce intraocular pressure but is often complicated by excessive tissue proliferation.
• Current treatments for post-surgical scarring have limitations.
• A sustained-release drug delivery system could improve surgical outcomes.

Purpose of the Study:

• To develop and evaluate a 5-fluorouracil (5-FU) loaded mesoporous poly(lactic) acid (PLA) delivery system.
• To assess its suitability for single subconjunctival implantation in glaucoma surgery.
• To investigate its antiproliferative effects and safety profile.

Main Methods:

• 5-FU was loaded into mesoporous PLA to create tablets (e.g., 1.5P15, 2.5P15).
• In vitro and in vivo release studies were conducted.
• Ocular toxicology, antiproliferative effects in rabbit models, and molecular analyses (Western blot for TGF-β, CTGF) were performed.

Main Results:

• Two 5-FU-PLA formulations (1.5P15, 2.5P15) showed optimal in vitro release profiles.
• In vivo studies confirmed safety and sustained release.
• 5-FU-PLA tablets significantly inhibited post-surgery tissue proliferation, improved surgical success, and provided longer-lasting inhibition of TGF-β and CTGF compared to free 5-FU.

Conclusions:

• 5-FU-PLA tablets offer sustained release of 5-FU.
• This system is suitable for single subconjunctival implantation.
• It effectively inhibits proliferation and enhances success rates in glaucoma filtration surgery.