High Throughput Screening of Valganciclovir in Acidic Microenvironments 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 in...
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doaj-534fd86a8bb540caba28ace9e1bf70412020-11-24T22:41:44ZengMDPI AGMaterials1996-19442015-04-01841714172810.3390/ma8041714ma8041714High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin FilmsTeilo Schaller0Tobias Wenner1Rupesh Agrawal2Stephen Teoh3Li Ting Phua4Joachim S. C. Loo5Terry W. J. Steele6School of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, SingaporeSchool of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, SingaporeNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, SingaporeNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, SingaporeSchool of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, SingaporeSchool of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, SingaporeSchool of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, SingaporeGanciclovir 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.http://www.mdpi.com/1996-1944/8/4/1714poly(lactic-co-glycolic acid) (PLGA)polymeric biomaterialsophthalmic drug deliveryhigh-throughputfluorescence spectroscopydrug-excipient interaction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Teilo Schaller Tobias Wenner Rupesh Agrawal Stephen Teoh Li Ting Phua Joachim S. C. Loo Terry W. J. Steele |
spellingShingle |
Teilo Schaller Tobias Wenner Rupesh Agrawal Stephen Teoh Li Ting Phua Joachim S. C. Loo Terry W. J. Steele High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films Materials poly(lactic-co-glycolic acid) (PLGA) polymeric biomaterials ophthalmic drug delivery high-throughput fluorescence spectroscopy drug-excipient interaction |
author_facet |
Teilo Schaller Tobias Wenner Rupesh Agrawal Stephen Teoh Li Ting Phua Joachim S. C. Loo Terry W. J. Steele |
author_sort |
Teilo Schaller |
title |
High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films |
title_short |
High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films |
title_full |
High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films |
title_fullStr |
High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films |
title_full_unstemmed |
High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films |
title_sort |
high throughput screening of valganciclovir in acidic microenvironments of polyester thin films |
publisher |
MDPI AG |
series |
Materials |
issn |
1996-1944 |
publishDate |
2015-04-01 |
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. |
topic |
poly(lactic-co-glycolic acid) (PLGA) polymeric biomaterials ophthalmic drug delivery high-throughput fluorescence spectroscopy drug-excipient interaction |
url |
http://www.mdpi.com/1996-1944/8/4/1714 |
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