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Title: A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model
Authors: Liu, Yu-Chi
Ng, Xu Wen
Teo, Ericia Pei Wen
Ang, Heng-Pei
Lwin, Nyein Chan
Chan, Nicole Shu Wen
Venkatraman, Subbu S.
Wong, Tina Tzeeling
Mehta, Jodhbir Singh
Keywords: Allergic Conjunctivitis
Issue Date: 2018
Source: Liu, Y.-C., Ng, X. W., Teo, E. P. W., Ang, H.-P., Lwin, N. C., Chan, N. S. W., et al. (2018). A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model. Investigative Ophthalmology & Visual Science, 59(2), 675-684.
Series/Report no.: Investigative Ophthalmology & Visual Science
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 were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. 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). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results: The microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups 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). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions: Tacrolimus-loaded microfilms display good biocompatibility and desirable sustained drug release. 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.
ISSN: 0146-0404
Rights: © 2018 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
Fulltext Permission: open
Fulltext Availability: With Fulltext
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