Treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system

Wenqiang Liu, Anessa Puskar Tawakol, Kayla M. Rudeen, William F. Mieler, Jennifer J. Kang-Mieler

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Purpose: To evaluate the in vivo treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system (DDS) in a laser-induced choroidal neovascularization (CNV) rat model. Methods: Two weeks after CNV induction, animals were randomly assigned into four experimental groups: (1) no treatment, (2) single intravitreal (IVT) injection of blank DDS, (3) bimonthly bolus IVT aflibercept injections, and (4) single IVT injection of aflibercept-DDS. CNV lesion sizes were monitored longitudinally using fluorescence angiography and multi-Otsu thresholding for 6 months. For safety and biocompatibility assessment, an additional three non-CNV animals received a blank DDS injection. Electroretinogram, intraocular pressure, and clinical ophthalmoscopic examinations were performed. Results: The average lesion areas at week 0 (treatment intervention) were (1) 8693 ± 628 μm2 for no treatment, (2) 8261 ± 709 μm2 for blank DDS, (3) 10,368 ± 885 μm2 for bolus, and (4) 10,306 ± 1212 μm2 for aflibercept-DDS. For the nontreated groups, CNV lesion size increased by week 2 and remained increased throughout the study. The treated groups exhibited CNV size reduction after week 2 and remained for 6 months. At week 22, the average percent changes in CNV lesion area were +38.87% ± 7.08%, +34.19% ± 9.93%, –25.95% ± 3.51%, and –32.69% ± 5.40% for the above corresponding groups. No signs of chronic inflammation and other ocular abnormalities were found. Conclusions: The aflibercept-DDS was effective in treating CNV lesions for 6 months and is safe, well tolerated, and biocompatible. Translational Relevance: The proposed DDS is a promising system to reduce IVT injection frequency for anti–vascular endothelial growth factor treatment.

Original languageEnglish
Article number13
Pages (from-to)1-14
Number of pages14
JournalTranslational Vision Science and Technology
Volume9
Issue number11
DOIs
StatePublished - Oct 2020

Keywords

  • Anti-VEGF treatment
  • Drug delivery system
  • In vivo safety
  • Laser-induced CNV
  • Sustained release

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