Abstract
Purpose: :
5–FU injections are used to modulate the wound healing response following trabeculectomy. However, injections may be frequent especially in cases of a marked scarring response. The optimum therapeutic effect 5–FU is currently limited by its delivery as an aqueous solution. We have previously shown that the duration of antiscarring action on fibroblasts is dependent on the time and concentration of exposure to 5–FU. We hypothesised that the prolonged release of 5–FU can be achieved by using commercially available hyaluronic acid (HA) as a delivery system. Prolonged release profiles of 5FU–HA formulations were investigated.
Methods: :
The release profile of 5–FU–HA formulations was investigated using an infusion machine supplying flow rates ranging 2–20ul/min through a 200ul test chamber. Clinical 5–FU (50ug/ml) and HA were mixed and injected into the infusion chamber. Three clinical HA formulations were used (Healon, Healon GV and Healon5) The outflow solution was collected and analysed. The release profile of 5–FU solution alone served as control. Rate of drug release was compared with rabbit conjunctival tissue that was placed in the chamber and injected with 5FU– HA formulations.
Results: :
The amount of 5–FU released was prolonged as the relative amount of HA increased. Release rates were notably reduced when 5–FU–HA was injected into tissue (e.g. 3.8mg/ml compared to 6.5mg/ml for Healon; 2.3 mg/ml compared to 5.3mg/ml for Healon GV and 0.45mg/ml compared to 2.3mg/ml for Healon 5). Prolonged release periods of 3 hours (70% total 5–FU) were observed from tissue for all of the three HA solutions when injected into tissue. Without HA, 70% 5–FU was released in 1 hour.
Conclusions: :
The data confirm that 5–FU–HA formulation prolongs drug release from tissue by at least 2 fold depending on HA. The 5–FU release profile is influenced by HA viscosity since higher concentrations and molecular weights of HA prolonged 5–FU release. This novel delivery method has the potential to improve the therapeutic index of 5FU and provide greater efficacy in the treatment and prevention of bleb failure.
Keywords: wound healing • pharmacology • injection