Sustained Prednisolone Acetate-loaded Microfilm Drug Delivery System Effectively Prolongs corneal allograft survival in the rat keratoplasty model

Abstract

 

Purpose

 

To investigate the efficacy of a sustained prednisolone acetate (PA)-loaded poly (d,l-lactide-co-ε-caprolactone) (PLC) microfilm drug delivery system (DDS) for promoting the survival of allogeneic rat corneal grafts after penetrating keratoplasty (PK).

 

Methods

 

A total of 48 PK were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: group 1 (n=12), syngeneic control; group 2 (n=12), allogeneic control without treatment; group 3 (n=12), allogeneic grafts with subconjunctivally-implanted PA-loaded microfilm treatment; group 4 (n=12): allogeneic grafts with 1% PA eye drops treatment. All grafts were evaluated for 28 days by a scoring rejection index (RI), assessing graft opacity, edema and neovascularization by slit lamp biomicroscopy and anterior segment optical coherence tomography (ASOCT). Time to rejection was analyzed with Kaplan-Meier survival analysis. PA concentrations in the aqueous humor were measured using high-performance liquid chromatography. Histopathological and immunohistochemical staining were also performed.

 

Results

 

The PA-loaded microfilms achieved a sustained and steady release at a rate of 7.0ug/day, with a consistent drug concentration of 207-209 ng/ml in the aqueous. The mean survival was >28 days in group 1, 9.9±0.8 days in group 2, 26.8±2.7 days in group 3 (P = 0.023 as compared with group 2), and 26.4±3.4 days in group 4 (P = 0.027 as compared with group 2). Statistically significant decrease in CD4+, CD8+, CD163+, CD11c+, CD 25+ and CD54+ cell infiltration in group 3 as compared with group 2 was observed on immunohistochemistry (P<0.001). There was no significant difference between group 3 and group 4 in the mean survival and immunohistochemical analysis.

 

Conclusions

 

The sustained PA-loaded microfilm DDS effectively prolongs corneal allograft survival in the rat model. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

 

 

Figure 1: Representative slit lamp biomicroscopy and ASOCT photos showing the status of the corneal grafts 2 and 4 weeks after penetrating keratoplasty

 

 

Figure 2: Kaplan-Meier analysis of the rejection-free graft survival

 

Keywords: 487 corticosteroids