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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Main Authors: Teilo Schaller, Tobias Wenner, Rupesh Agrawal, Stephen Teoh, Li Ting Phua, Joachim S. C. Loo, Terry W. J. Steele
Format: Article
Language:English
Published: MDPI AG 2015-04-01
Series:Materials
Subjects:
Online Access:http://www.mdpi.com/1996-1944/8/4/1714
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spelling 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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