A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model

Abstract

Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-ε-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

Use of Anterior Segment Optical Coherence Tomography to Predict Corneal Graft Rejection in Small Animal Models

“…4 However, this is graded subjectively, and it can be difficult, especially in cases of mild edema or when the severity of graft opacity or neovascularization varies in different regions of the transplanted cornea. 5 In our previous study using a rat PK model, 6 we also encountered this problem in diagnosing graft rejection. Flynn et al, 5 therefore, reported the use of in vivo graft pachymetry as a useful tool to objectively diagnose graft rejection in a mouse model of corneal transplantation.…”

“…Rats were adequately anesthetized, and then orthotropic corneal transplantation was performed as previously described. 6 In brief, corneal donor grafts with a diameter of 3.5 mm were obtained. After the recipient corneas were removed with a 3-mm trephine, the grafts were transplanted onto the recipients with eight 10-0 nylon interrupted sutures.…”

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

“…It would only require a simple implantation process into the vitreous cavity close to the limbus of the eye, and would not require suturing after implantation. Recently, there has been an emergence in several novel delivery systems, such as encapsulated cell technology (ECT) 24,25 , hydrogels 26 , and microfilms 27 . However, the method used in the current study for preparing and delivering the drug-resin complex is both easy to follow and inexpensive, thereby being more advantageous for use in a basic research environment.…”

A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model

“…14,15 Our previous work has shown that subconjunctival poly [d,l-lactide-co-e-caprolactone] (PLC) microfilms were biodegradable and displayed good biocompatibility and feasibility. 16 We further loaded the PLC microfilms with prednisolone acetate (PA) and demonstrated that the PA microfilms significantly reduced corneal graft rejection after corneal transplantation, 17 reduced postoperative inflammation and prolonged bleb survival following glaucoma filtering surgery, 18 and suppressed the severity of uveitis in animal models. 19 We have also loaded the PLC microfilms with timolol maleate and demonstrated the sustained intraocular pressurelowering effects.…”