A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model
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 characteri...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/88206 http://hdl.handle.net/10220/44577 |
| _version_ | 1826114498351595520 |
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| author | 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 |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering 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 |
| author_sort | Liu, Yu-Chi |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:40:28Z |
| format | Journal Article |
| id | ntu-10356/88206 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:40:28Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/882062023-03-04T17:11:35Z A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model 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 School of Materials Science & Engineering School of Mechanical and Aerospace Engineering Allergic Conjunctivitis Tacrolimus 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. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version 2018-03-16T06:49:14Z 2019-12-06T16:58:16Z 2018-03-16T06:49:14Z 2019-12-06T16:58:16Z 2018 2018 Journal Article 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. 0146-0404 https://hdl.handle.net/10356/88206 http://hdl.handle.net/10220/44577 10.1167/iovs.17-23066 203629 en Investigative Ophthalmology & Visual Science © 2018 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License 10 p. application/pdf |
| spellingShingle | Allergic Conjunctivitis Tacrolimus 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 A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title | A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title_full | A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title_fullStr | A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title_full_unstemmed | A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title_short | A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model |
| title_sort | biodegradable sustained released tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model |
| topic | Allergic Conjunctivitis Tacrolimus |
| url | https://hdl.handle.net/10356/88206 http://hdl.handle.net/10220/44577 |
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