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

To develop a 5-fluorouracil (5-FU) mesoporous poly(lactic) acid (PLA) delivery system for glaucoma filtration surgery suitable for a single subconjunctival implantation.

The 5-FU was infiltration-loaded into mesoporous PLA. In vitro and in vivo release experiments and ocular toxicology evaluation of the formulation were performed. The antiproliferative effect of this 5-FU-PLA tablet after glaucoma filtration surgery in rabbits was evaluated. Pathology, immunohistochemistry, and Western blot were used to further validate the inhibitory effect of this sustained release system.

Various drug formulations were tested, and two 5-FU-PLA tablets, namely 1.5P15 (5-FU 1.5 mg+PLA 15 000 Da) and 2.5P15 (5-FU 2.5 mg+PLA 15 000 Da), had the most suitable release profiles in vitro. Further in vivo studies confirmed the safety and sustained-release profiles of both drugs. Both 5-FU-PLA tablets, relative to the free drugs, significantly inhibited tissue proliferation after glaucoma filtration and improved surgical success. Western blot showed that transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) were inhibited by 5-FU after filtration surgery, with the effects of the 5-FU-PLA tablets being more lasting.

The tested 5-FU-PLA tablets provide a sustained release of 5-FU, which may be used for a single subconjunctival implantation to inhibit proliferation after filtration surgery.