Controlled and Extended In Vitro Release of Bioactive Anti-Vascular Endothelial Growth Factors from a Microsphere-Hydrogel Drug Delivery System

Current Eye Research
Christian R Osswald, Jennifer J Kang-Mieler

Abstract

To demonstrate controlled and extended release of bioactive anti-vascular endothelial growth factor (VEGF) agents (ranibizumab or aflibercept) from an injectable microsphere-hydrogel drug delivery system (DDS). Anti-VEGF agents were radiolabeled with iodine-125 and loaded into poly(lactic-co-glycolic acid) (PLGA) 75:25 microspheres using a modified double-emulsion, solvent evaporation technique. Microspheres were then suspended in an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel to create a microsphere-hydrogel DDS. Release profiles were performed in phosphate buffered saline at 37°C and at predetermined intervals, release samples were collected. Microspheres were also made using non-radiolabeled anti-VEGFs to determine the bioactivity of the DDS throughout release. Bioactivity and cytotoxicity of release samples were determined using human umbilical vascular endothelial cells (HUVECs) under VEGF-induced proliferation. The DDS is capable of releasing either ranibizumab or aflibercept for 196 days with an initial burst (first 24 h) of 22.2 ± 2.2 and 13.1 ± 0.5 μg, respectively, followed by controlled release of 0.153 and 0.065 μg/day, respectively. Release samples showed no toxicity in HUVECs at any tim...Continue Reading

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Citations

Nov 8, 2016·Drug Discovery Today·Krishna RadhakrishnanRupesh Agrawal
May 31, 2017·Current Eye Research·Christian R OsswaldJennifer J Kang-Mieler
Jun 20, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Muhammed AnwaryViness Pillay
Oct 26, 2018·Expert Opinion on Drug Delivery·Hui Yee ChuaSubbu Venkatraman
Mar 25, 2019·Drug Delivery·Asitha BalachandraPeter van Wijngaarden
Feb 12, 2017·Nanomedicine·Rini Rachel Joseph, Subbu S Venkatraman
Dec 6, 2017·Macromolecular Bioscience·Sahar AwwadSteve Brocchini
Jun 19, 2019·Nanomaterials·Simona SapinoMarina Gallarate
Aug 24, 2016·Expert Opinion on Drug Delivery·Jennifer J Kang-MielerWilliam F Mieler
Feb 1, 2019·Translational Vision Science & Technology·Wenqiang LiuJennifer J Kang-Mieler
Feb 20, 2020·Eye·Jennifer J Kang-MielerWilliam F Mieler
Jul 31, 2020·Journal of Drug Targeting·Rohit BishtJayabalan Nirmal
Jan 21, 2021·Pharmaceutics·Hyeong Min Kim, Se Joon Woo
Oct 30, 2020·Translational Vision Science & Technology·Wenqiang LiuJennifer J Kang-Mieler
Jan 18, 2018·Advanced Drug Delivery Reviews·Abhirup MandalAshim K Mitra

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