Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix

摘要

A subtenon injection of triamcinolone acetonide (TA) is a widely used treatment modality for various chorio-retinal diseases. Although it is less invasive than intravitreal injection, it can produce dose-associated ocular complications and has the disadvantages associated with systemic TA exposure. In this study we have developed and evaluated an episcleral film consisting of TA and poly-ε-caprolactone (PCL). The films were prepared by spraying a mixture of PCL in dichloromethane and TA in acetone. The films were produced as 6 mm wide and 12 mm long episcleral plaques. X-ray diffraction demonstrated an even distribution of TA crystals in PCL, although the TA was less crystalized than a native TA control. Fourier transform infrared spectroscopy revealed effective integration of TA within the PCL matrix. An in vitro study of the release of TA from the episcleral plaques showed that TA release rate was only 40-50% that of the equivalent native TA control. An in vivo study demonstrated that the plaques were well tolerated in rabbit eyes with significantly less systemic TA exposure. The episcleral plaques provided therapeutic vitreous TA levels for 3 months, while TA levels in the vitreous were detectable for only 1 month following an equivalent dose by subtenon TA injection. The PCL-TA 30-60 episcleral plaque may be further developed as a better alternative treatment for many chronic vitreo-retinal diseases, providing longer and controlled release and fewer drug-associated complications than those associated with a conventional subtenon injection of TA.