Purpose In previous studies, we confirmed that the foldable capsular vitreous body (FCVB) could serve as a drug delivery system (DDS), in addition to a vitreous substitute. In this study, we furtherevaluated the characteristics of FCVB release of 5-fluorouracil (5-Fu) in vitro and in vivo.
Methods For thein vitro study,5-Fu at concentrations of 50, 100, and 200 μg/ml were injected into FCVB capsules, which were immersed in cups of modified Franz diffusion cells; 400 μl of liquid was aspirated at time intervals of 20, 40, 60, 120, 180, 240, 300 and 360 minutes.In thein vivo study, FCVB was folded and implanted into the vitreous cavity of five rabbits, and then 1.0 ml 5-Fu (200 μg/ml) was injected into the capsule. Intravitreal injections were performed on another five rabbits as the controls. Aqueous humor was aspirated at postoperative 0.5 h, 3, 7, 14, 28, 42, and 56 days. The 5-Fu contents in vitro were detected by UV spectrophotometry and Ultra Performance Liquid Chromatography (UPLC), while the 5-Fu contents in aqueous humor were only detected by UPLC. The stock solution in the FCVB before-release study and the residue in FCVB were collected for UPLC analysis.
Results UV spectrophotometry showed FCVB release of 5-Fu in a time-dependent manner and in a dose-dependent manner with three dosages of 50, 100, and 200 μg/ml at time intervals from 20 to 360 min in vitro, while 5-Fu was only released sustainably from FCVB by UPLC analysis. The 5-Fu contents in the aqueous humor were detected until D56 with sustained release during postoperative D3–56. However, the 5-Fu contents were detected until D7 and were undetectable on D14 in the controls. At the end of release studies, 2.7%, 6.8%, 6.5% of 5-Fu was released from FCVB in the 50, 100, and 200 μg/ml groups, respectively, and 48.8% of 5-Fu was released within postoperative D56 in vivo.
Conclusions FCVB can also release 5-Fu sustainably and mechanically,indicating that FCVB can be used as a common vehicle for sustainably releasing different drugs and a valuable pharmaceutical adjunctive therapy to conventional vitreous surgery in managing or preventing proliferative vitreoretinopathy. |
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