Abstract
Purpose: :
It was demonstrated that activin receptor-like kinase 5 (ALK-5) inhibitors are effective in suppressing expression of downstream, scarring-related proteins of transforming growth factor-β in both in vitro and in vivo. The purpose of this study is to investigate the poly(lactic-co-glycolic acid)-polyethelene glycol- poly(lactic-co-glycolic acid) [PLGA-PEG-PLGA] polymer based thermoreversible gel for controlled delivery of the inhibitor for glaucoma filtration surgery (GFS).
Methods: :
Thermoreversible gel of PLGA-PEG-PLGA polymer containing ALK-5 inhibitor SB-505124 was developed after dissolving PLGA-PEG-PLGA in the water (30 % w/v) at 4 ºC. The visual observation and test tube inversion method were used to study the temperature at which gel is formed over heating the polymer solution from 10 to 45 ºC. The in vitro drug release of the gel was studied using dialysis cassette method. In an in vivo rabbit GFS model, the gel containing 10 mg SB-505124 was delivered during the surgery. Filtering blebs were observed and imaged until the time of bleb failure after the surgery. The period of bleb survival was statistically evaluated with Kaplan-Meier analysis.
Results: :
The PLGA-PEG-PLGA gel showed sol-gel transition from low temperature (10 ºC) to body temperature (37 ºC). The visual observation and test tube inversion methods showed that the polymer solution showed complete gel formation at 37 ºC. The in vitro drug release study showed controlled drug release up to 20 days. Filtering blebs treated with gel containing SB-505124 were maintained for more than 2 weeks while all blebs were failed within 6 days in control. The period of bleb survival was significantly longer in eyes treated with SB-505124 than that in controls (n=3 in each group, log rank=5.012, p<0.05). Severe post surgical complications were not observed.
Conclusions: :
The PLGA-PEG-PLGA based thermoreversible gel system was successful for controlled delivery of the inhibitor SB-505124 and may provide a novel controlled delivery system in GFS.