Abstract
Purpose: :
Celecoxib (CXB), a COX-2 inhibitor, has been shown to inhibit posterior capsular opacification (PCO) in vitro (Chandler HL, et al. Mol Vis. 2007;13:677-691). The purpose of this study was to determine if acrylic IOLs could be used to deliver sustained release of CXB in vitro at sufficient levels to inhibit PCO.
Methods: :
Hydrophobic (HPB - AMO, Irvine, CA) or hydrophilic acrylic IOLs (HPL - Acri.Tec, Berlin Germany) were placed in 5 ml of 100µM CXB solution or PBS for 1, 8 or 24 hours, in triplicate. The IOLs were transferred to individual vials containing 1 mL of PBS (pH 7.4) and maintained in a water bath at 37°C. IOLs were removed and placed into new vials with 1 ml PBS every 24 hours for 7 consecutive days. CXB concentrations in the PBS were performed using a reversed-phase high-performance liquid chromatography (HPLC) assay and reported as µg of drug release/day.
Results: :
With HPB and HPL IOLs, there was increased release of CXB with longer time of incubation. IOLs (HPB and HPL) incubated for 24 hours had significantly increased rates of CXB release compared to PBS, 1 and 8-hour incubations (P<0.001). HPL IOLs had similar release rate of CXB during the first 24 hours (mean 1.4 ± SD 0.4 ug/day) compared to HPB IOLs (mean 1.1 ± SD 0.7 ug/day), and also through 7 days (HPL: mean 0.4 ± SD 0.1 ug/day; HPB: mean 0.3 ± SD 0.1 ug/day). Mean cumulative release of CXB from HPL and HBP IOLs over 7 days was 4.4 ± SD 1.1 ug and 3.6 ± SD 1.4 ug. Concentrations of CXB that could be achieved in vitro in a 250 µl (human lens capsule volume) using CXB-incubated IOLs were 14.5 (24 hours) to 4 micromolar (7 days).
Conclusions: :
Incubating acrylic IOLs in 100µM of CXB solution allowed sustained release of CXB for at least 7 days at levels that may inhibit PCO. There were no significant differences in CXB release rates between HPB and HPL IOLs. Based on these results, use of CXB-incubated IOLs may be an effective method to prevent PCO.
Keywords: posterior capsular opacification (PCO) • intraocular lens • inflammation