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Materials 2015, 8(4), 1714-1728; doi:10.3390/ma8041714

High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films

1
School of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, Singapore
2
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Carsten Werner
Received: 1 December 2014 / Revised: 19 March 2015 / Accepted: 30 March 2015 / Published: 13 April 2015
(This article belongs to the Special Issue Materials for Drug Delivery)
View Full-Text   |   Download PDF [635 KB, uploaded 13 April 2015]   |  

Abstract

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. View Full-Text
Keywords: poly(lactic-co-glycolic acid) (PLGA); polymeric biomaterials; ophthalmic drug delivery; high-throughput; fluorescence spectroscopy; drug-excipient interaction poly(lactic-co-glycolic acid) (PLGA); polymeric biomaterials; ophthalmic drug delivery; high-throughput; fluorescence spectroscopy; drug-excipient interaction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Schaller, T.; Wenner, T.; Agrawal, R.; Teoh, S.; Phua, L.T.; Loo, J.S.C.; Steele, T.W.J. High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films. Materials 2015, 8, 1714-1728.

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