TY - JOUR
T1 - Treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system
AU - Liu, Wenqiang
AU - Tawakol, Anessa Puskar
AU - Rudeen, Kayla M.
AU - Mieler, William F.
AU - Kang-Mieler, Jennifer J.
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Anti-VEGF treatment
KW - Drug delivery system
KW - In vivo safety
KW - Laser-induced CNV
KW - Sustained release
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U2 - 10.1167/tvst.9.11.13
DO - 10.1167/tvst.9.11.13
M3 - Article
AN - SCOPUS:85097400840
VL - 9
SP - 1
EP - 14
JO - Translational Vision Science and Technology
JF - Translational Vision Science and Technology
IS - 11
M1 - 13
ER -