High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films
Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated int...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/79382 http://hdl.handle.net/10220/26111 |
| _version_ | 1826121831750303744 |
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| author | Schaller, Teilo Wenner, Tobias Agrawal, Rupesh Teoh, Stephen Phua, Li Ting Loo, Joachim Say Chye Steele, Terry W. J. |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Schaller, Teilo Wenner, Tobias Agrawal, Rupesh Teoh, Stephen Phua, Li Ting Loo, Joachim Say Chye Steele, Terry W. J. |
| author_sort | Schaller, Teilo |
| collection | NTU |
| description | Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated intraocular injections, to improve compliance and to eliminate systemic side-effects, we investigated the tuning of the ganciclovir pro-drug valganciclovir and the release from thin films of poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or mixtures of both, as a step towards prototyping periocular valganciclovir implants. To investigate the drug release, we established and evaluated a high throughput fluorescence-based quantification screening assay for the detection of valganciclovir. Our protocol allows quantifying as little as 20 ng of valganciclovir in 96-well polypropylene plates and a 50× faster analysis compared to traditional HPLC measurements. This improvement can hence be extrapolated to other polyester matrix thin film formulations using a high-throughput approach. The acidic microenvironment within the polyester matrix was found to protect valganciclovir from degradation with resultant increases in the half-life of the drug in the periocular implant to 100 days. Linear release profiles were obtained using the pure polyester polymers for 10 days and 60 days formulations; however, gross phase separations of PCL and acid-terminated PLGA prevented tuning within these timeframes due to the phase separation of the polymer, valganciclovir, or both. |
| first_indexed | 2024-10-01T05:38:37Z |
| format | Journal Article |
| id | ntu-10356/79382 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:38:37Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/793822023-07-14T15:49:51Z High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films Schaller, Teilo Wenner, Tobias Agrawal, Rupesh Teoh, Stephen Phua, Li Ting Loo, Joachim Say Chye Steele, Terry W. J. School of Materials Science & Engineering DRNTU::Engineering::Materials Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated intraocular injections, to improve compliance and to eliminate systemic side-effects, we investigated the tuning of the ganciclovir pro-drug valganciclovir and the release from thin films of poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or mixtures of both, as a step towards prototyping periocular valganciclovir implants. To investigate the drug release, we established and evaluated a high throughput fluorescence-based quantification screening assay for the detection of valganciclovir. Our protocol allows quantifying as little as 20 ng of valganciclovir in 96-well polypropylene plates and a 50× faster analysis compared to traditional HPLC measurements. This improvement can hence be extrapolated to other polyester matrix thin film formulations using a high-throughput approach. The acidic microenvironment within the polyester matrix was found to protect valganciclovir from degradation with resultant increases in the half-life of the drug in the periocular implant to 100 days. Linear release profiles were obtained using the pure polyester polymers for 10 days and 60 days formulations; however, gross phase separations of PCL and acid-terminated PLGA prevented tuning within these timeframes due to the phase separation of the polymer, valganciclovir, or both. Published version 2015-06-29T02:25:26Z 2019-12-06T13:23:59Z 2015-06-29T02:25:26Z 2019-12-06T13:23:59Z 2015 2015 Journal Article Schaller, T., Wenner, T., Agrawal, R., Teoh, S., Phua, L. T., Loo, J. S. C., et al. (2015). High throughput screening of valganciclovir in acidic microenvironments of polyester thin films. Materials, 8(4), 1714-1728. 1996-1944 https://hdl.handle.net/10356/79382 http://hdl.handle.net/10220/26111 10.3390/ma8041714 en Materials © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | DRNTU::Engineering::Materials Schaller, Teilo Wenner, Tobias Agrawal, Rupesh Teoh, Stephen Phua, Li Ting Loo, Joachim Say Chye Steele, Terry W. J. High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title | High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title_full | High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title_fullStr | High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title_full_unstemmed | High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title_short | High throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| title_sort | high throughput screening of valganciclovir in acidic mircoenvironments of polyester thin films |
| topic | DRNTU::Engineering::Materials |
| url | https://hdl.handle.net/10356/79382 http://hdl.handle.net/10220/26111 |
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