Abstract
Abstract: :
Purpose: Intravitreous injection is one method to deliver drugs into vitreous cavity, but the demerit of this method is short duration of sustaind drug level and rapid elimination of the drug. Several drug delivery systems (DDS) have been developed recently, but they require operations with risk of severe complications. We confirmed the safety of injecting thermo–setting gel (TG), which gelates rapidly at body temperature, into the vitreous cavity (2003, ARVO). In this study, we examined the drug diffusion effect of TG in vitro and in vivo, and investigated the potential use of TG as a new DDS. Methods: We used two types of TG with different viscosities after gelation; low viscosity WTG–127 and high viscosity WTG–143(Wakamoto Pharmaceutical Co. Ltd.). In in vitro study, gelated WTG–127 (5 ml) containing Levofloxacin (LVFX) was soaked in PBS (50 ml) in a glass cylinder and kept at 40°C. The concentrations of LVFX in PBC were determined by HPLC at selected times. In in vivo study, white rabbits were treated as follows: (1) 0.5 ml of WTG–127 containing LVFX (1 mg/ml) was injected into vitreous cavity after aspiration of vitreous, (2) 0.1 ml of WTG–143 containing LVFX (5 mg/ml) was injected into vitreous cavity after aspiration of aqueous humor, (3) 0.1 ml of gelated WTG–143 containing LVFX (5 mg/ml) was injected into vitreous cavity after aspiration of aqueous humor. For the control, 0.1 ml of BSS plus® containing LVFX (5 mg/ml) was injected into vitreous cavity after aspiration of aqueous humor. The cocentrations of LVFX in aqueous humor and vitreous were determined by HPLC at selected times. Results: In in vitro studies, All the LVFX diffused from WTG in 3 weeks. In in vivo studies, the concentrations of LVFX were significantly higher in all WTG injections than in control in the vitreous at 1 day after injection (p<0.05), and in aqueous humor at 3 days after injection (p<0.05). LVFX was not detected in all cases at 7 days after injection. Conclusions: Elimination of the drug is more rapid in vivo than in vitro. Compared with injection of aqueous LVFX solution, injection of LVFX in WTG sustains the drug concentration for a longer period. TG may be a useful material as a drug delivery system for a short duration.
Keywords: vitreous substitutes • drug toxicity/drug effects • injection