September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model
Author Affiliations & Notes
  • Yu-Chi Liu
    Cornea and External Eye Disease, Singapore Eye Research Institute, Singapore, Singapore
  • Xu Wen Ng
    Nanyang Technological University, Singapore, Singapore
  • Heng Pei Ang
    Cornea and External Eye Disease, Singapore Eye Research Institute, Singapore, Singapore
  • Chan Nyein Lwin
    Singapore Eye Research Institute, Singapore, Singapore
  • Subbu Venkatraman
    Nanyang Technological University, Singapore, Singapore
  • Tina T Wong
    Singapore National Eye Centre, Singapore, Singapore
  • Jodhbir S Mehta
    Cornea and External Eye Disease, Singapore Eye Research Institute, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Yu-Chi Liu, None; Xu Wen Ng, None; Heng Pei Ang, None; Chan Nyein Lwin, None; Subbu Venkatraman, None; Tina Wong, None; Jodhbir Mehta, None
  • Footnotes
    Support  This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Programme (NMRC/TCR/1021-SERI/2013) and administered by the Singapore Ministry of Health’s National Medical Research Council.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4039. doi:
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      Yu-Chi Liu, Xu Wen Ng, Heng Pei Ang, Chan Nyein Lwin, Subbu Venkatraman, Tina T Wong, Jodhbir S Mehta; A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4039.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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