Evaluation of 5-fluorouracil released from a foldable capsular vitreous body in vitro and in vivo

Abstract

Previously, we have confirmed that the foldable capsular vitreous body (FCVB) can serve as a drug delivery system (DDS) as well as a vitreous substitute. Here, we evaluated the characteristics of the release of 5-fluorouracil (5-Fu) from FCVB in vitro and in vivo. For the in-vitro study, various concentrations of 5-FU (50-200μg/ml) were injected into FCVB capsules and immersed in cups of modified Franz diffusion cells, and liquid was aspirated at specific time intervals. In the in-vivo study, FCVB was folded and implanted into the vitreous cavity in the right eyes of five rabbits, and then 1.0ml 5-Fu (200μg/ml) was injected into the capsule. Another five rabbits that were used as the controls received intravitreal injections Aqueous humor was aspirated postoperatively at specific time intervals up to 56days. The 5-Fu contents in vitro were detected by UV spectrophotometry and ultra performance liquid chromatography (UPLC), and the in-vivo 5-FU levels in the aqueous humour were detected by UPLC. The stock solution in the FCVB before-release study and the FCVB residue were collected for UPLC analysis. UV spectrophotometry revealed that 5-FU was released from FCVB in vitro in a time-dependent manner from 20-360min in vitro. UPLC analysis revealed that 5-FU was released sustainably from FCVB. The 5-FU concentration in the aqueous humour was detected until postoperative day 56 (D56), with sustained release from postoperative days 3-56. However, the 5-FU concentration in the control samples was detected until only D7, and could not be detected on D14. Finally, 48.8% of the 5-FU was released on D56 in the in-vivo experiment. FCVB can release 5-Fu sustainably and mechanically, indicating that FCVB can be used as a common vehicle for the sustainable release of different drugs. FCVB is a potentially valuable pharmaceutical adjunct to conventional vitreous surgery for managing or preventing proliferative vitreoretinopathy.