Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques
A clinical need exists for more effective intravitreal (IVT) drug delivery systems (DDS). This study tested the hypothesis that a novel biodegradable, injectable microsphere-hydrogel drug delivery system loaded with aflibercept (aflibercept-DDS) would exhibit long-term safety and biocompatibility in...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2025.2460671 |
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| author | Brett D. Story Sangwan Park Karolina Roszak Jaeho Shim Monica Motta Michelle Ferneding Kayla M. Rudeen Andrew Blandino Monica Ardon Sophie Le Leandro B. C. Teixeira Glenn Yiu William F. Mieler Sara M. Thomasy Jennifer J. Kang-Mieler |
| author_facet | Brett D. Story Sangwan Park Karolina Roszak Jaeho Shim Monica Motta Michelle Ferneding Kayla M. Rudeen Andrew Blandino Monica Ardon Sophie Le Leandro B. C. Teixeira Glenn Yiu William F. Mieler Sara M. Thomasy Jennifer J. Kang-Mieler |
| author_sort | Brett D. Story |
| collection | DOAJ |
| description | A clinical need exists for more effective intravitreal (IVT) drug delivery systems (DDS). This study tested the hypothesis that a novel biodegradable, injectable microsphere-hydrogel drug delivery system loaded with aflibercept (aflibercept-DDS) would exhibit long-term safety and biocompatibility in a non-human primate (NHP) model. We generated aflibercept-loaded poly (lactic-co-glycolic acid) microparticles with a modified double emulsion technique then embedded them into a biodegradable, thermo-responsive poly (ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide hydrogel. Aflibercept-DDS (50 µL, 15 µg) was injected into the right eye of 23 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP), corneal pachymetry, specular microscopy, A-scan biometry, streak retinoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and electroretinography (ERG) were performed monthly. Globes from 7 NHPs were histologically examined. Aflibercept-DDS was visualized in the vitreous up to 9 months post-IVT injection, slightly impeding fundoscopy in 4 of 23 eyes; no other consistent abnormalities were appreciated during ophthalmic examination. The IOP and total retinal thickness remained normal in all animals over all timepoints. Central corneal thickness, endothelial cell density, axial globe length, and refractive error did not significantly differ from baseline. Scotopic mixed rod-cone implicit times and amplitudes along with photopic cone response implicit times and amplitudes did not significantly differ from control values. No retinal or choroidal vascular abnormalities were detected with FA and normal retinal architecture was preserved using SD-OCT. Intravitreal injection of a biodegradable aflibercept-DDS was safe and well tolerated in NHPs up to 24 months. |
| format | Article |
| id | doaj-art-7b409d8f16dc48d3b95d01f954641abe |
| institution | OA Journals |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-7b409d8f16dc48d3b95d01f954641abe2025-08-20T02:29:59ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642025-12-0132110.1080/10717544.2025.2460671Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaquesBrett D. Story0Sangwan Park1Karolina Roszak2Jaeho Shim3Monica Motta4Michelle Ferneding5Kayla M. Rudeen6Andrew Blandino7Monica Ardon8Sophie Le9Leandro B. C. Teixeira10Glenn Yiu11William F. Mieler12Sara M. Thomasy13Jennifer J. Kang-Mieler14Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USADepartment of Statistics, University of California, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USADepartment of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA, USADepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois, Chicago, IL, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA, USADepartment of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USAA clinical need exists for more effective intravitreal (IVT) drug delivery systems (DDS). This study tested the hypothesis that a novel biodegradable, injectable microsphere-hydrogel drug delivery system loaded with aflibercept (aflibercept-DDS) would exhibit long-term safety and biocompatibility in a non-human primate (NHP) model. We generated aflibercept-loaded poly (lactic-co-glycolic acid) microparticles with a modified double emulsion technique then embedded them into a biodegradable, thermo-responsive poly (ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide hydrogel. Aflibercept-DDS (50 µL, 15 µg) was injected into the right eye of 23 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP), corneal pachymetry, specular microscopy, A-scan biometry, streak retinoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and electroretinography (ERG) were performed monthly. Globes from 7 NHPs were histologically examined. Aflibercept-DDS was visualized in the vitreous up to 9 months post-IVT injection, slightly impeding fundoscopy in 4 of 23 eyes; no other consistent abnormalities were appreciated during ophthalmic examination. The IOP and total retinal thickness remained normal in all animals over all timepoints. Central corneal thickness, endothelial cell density, axial globe length, and refractive error did not significantly differ from baseline. Scotopic mixed rod-cone implicit times and amplitudes along with photopic cone response implicit times and amplitudes did not significantly differ from control values. No retinal or choroidal vascular abnormalities were detected with FA and normal retinal architecture was preserved using SD-OCT. Intravitreal injection of a biodegradable aflibercept-DDS was safe and well tolerated in NHPs up to 24 months.https://www.tandfonline.com/doi/10.1080/10717544.2025.2460671afliberceptanti-VEGFcontrolled drug deliveryintravitreal injectionnonhuman primatethermo-responsive hydrogel |
| spellingShingle | Brett D. Story Sangwan Park Karolina Roszak Jaeho Shim Monica Motta Michelle Ferneding Kayla M. Rudeen Andrew Blandino Monica Ardon Sophie Le Leandro B. C. Teixeira Glenn Yiu William F. Mieler Sara M. Thomasy Jennifer J. Kang-Mieler Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques Drug Delivery aflibercept anti-VEGF controlled drug delivery intravitreal injection nonhuman primate thermo-responsive hydrogel |
| title | Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques |
| title_full | Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques |
| title_fullStr | Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques |
| title_full_unstemmed | Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques |
| title_short | Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques |
| title_sort | safety and biocompatibility of a novel biodegradable aflibercept drug delivery system in rhesus macaques |
| topic | aflibercept anti-VEGF controlled drug delivery intravitreal injection nonhuman primate thermo-responsive hydrogel |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2025.2460671 |
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