Abstract
Purpose :
To investigate the drug release profiles of a tacrolimus-loaded poly (d,l-lactide-co-ε-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model.
Methods :
The in vitro and in vivo drug release profiles of tacrolimus-loaded microfilms were first characterized using high-performance liquid chromatography. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution applications. The mice were divided into six groups (n = 12 in each): negative control (NC), positive control (PC), tacrolimus eye drops (Te), subconjunctival tacrolimus microfilm (Tm), dexamethasone eye drops (De), and tacrolimus + dexamethasone eye drops (Te+De) groups. The mice were evaluated for 28 days by a scoring system, assessing the conjunctival redness, chemosis, lid edema and tearing. Histopathological and immunohistochemical staining with CD11c, CD4 and interleukin (IL)-4 were performed.
Results :
The microfilms were biocompatible and delivered clinically sufficient tacrolimus dose in a sustained manner over 6 weeks, with a steady rate of 0.212-0.243 μg/day in vivo. As compared to the PC groups, all the groups had significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De and Te+De groups, respectively, at 4 weeks after treatment), with no significant difference between the Te and Tm group. The suppressed CD11c, CD4 and IL-4 expression were also observed in the Te, Tm, De and Te+De groups, with more reduction in the expression in the Te+De group.
Conclusions :
Tacrolimus-loaded microfilms display good biocompatibility and desirable sustained drug release profiles. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.