Evaluation of prednisolone-acetate (PA) loaded microfilm in a rabbit model of recurrent uveitis

Abstract

 

Purpose

 

To investigate the efficacy of biodegradable PA-loaded microfilms in a rabbit model of uveitis.

 

Methods

 

PA-loaded microfilms were fabricated by entrapping PA in biodegradable poly [d,l-lactide-co-ε-caprolactone] (PLC) via solvent casting. High performance liquid chromatography was used to determine PA release in vitro at 37 °C for 60 days. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen in pre-immunized rabbits. A randomized placebo controlled study was carried out on uveitis model rabbits assigned to receive either PA-loaded or blank microfilms. Seven days after the induction, PA-loaded and blank microfilms were implanted subconjunctivally into the respective treatment and placebo arms. Inflammatory scoring was evaluated by observations of anterior chamber activity, vitreous haze and iris vessels with grading system using slit lamp examination and fundus examination for 28 days. Histological examination of the enucleated eyes was performed at the end of the study. An estimate of PA release in vivo was calculated from measured residual PA amounts in microfilms retrieved after the rabbits were sacrificed.

 

Results

 

Sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded microfilms. This formulation was selected for in vivo evaluation as we postulate that it would best match our desired dose for clinical use. From the in vitro/ in vivo correlations, an estimate of 0.16mg of PA was released in vivo for the first 4 days followed by release of 0.08mg of PA, which adequately matched the commercial available steroid ophthalmic drops that are currently used for uveitis treatment. Animals implanted with PA-microfilms exhibited significantly lowered median inflammatory score when compared against the placebo group (P=0.007). Histology results confirmed that there was no significant scarring or inflammation around the microfilm.

 

Conclusions

 

PA microfilms developed in this study maintained a release of clinically therapeutic levels of PA, which was effective in suppressing inflammation in the rabbit model of uveitis.

 

 

Figure 1 Median inflammatory scores in (a) control group and (b) treatment group; (c) Combined inflammatory score

 

 

Figure 2 Histology images of the iris and ciliary body stained with Picosirius red. (A) Eye implanted with blank microfilm. (B) Eye implanted with PA-loaded microfilm.

 

Keywords: 746 uveitis-clinical/animal model