Evidence map›Paper›PMID 40038090›Full record

ArticleDrug delivery2025

Safety and biocompatibility of a novel biodegradable aflibercept-drug delivery system in rhesus macaques.

Brett D Story, Sangwan Park, Karolina Roszak, Jaeho Shim, Monica Motta, Michelle Ferneding, Kayla M Rudeen, Andrew Blandino, Monica Ardon, Sophie Le and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug delivery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Brett D StoryDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Sangwan ParkDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Karolina RoszakDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Jaeho ShimDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Monica MottaDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Michelle FernedingDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Kayla M RudeenDepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
Andrew BlandinoDepartment of Statistics, University of California, Davis, CA, USA.
Monica ArdonDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Sophie LeDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Leandro B C TeixeiraDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Glenn YiuDepartment of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA, USA.
William F MielerDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois, Chicago, IL, USA.
Sara M ThomasyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Jennifer J Kang-MielerDepartment of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
VISION RESEARCH CORE GRANTP30EY012576 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI LISA M OAKES · 1999 to 2026
$18.9M
Novel Model Systems for the Study of Cone Disorders and Other Heritable Retinal DiseasesU24EY029904 · NEI · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI, ROGERS, JEFFREY A. · 2018 to 2023
$7.7M
Diversity Supplement: Advancing novel therapies for optic neuropathy with a nonhuman primate modelR01EY033733 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Sara Michelle Thomasy · 2023 to 2026
$2.9M
Sustained Ocular Drug Delivery System for Anti-VEGF AgentsR01EY029298 · NEI · THE TRUSTEES OF THE STEVENS INSTITUTE OF TECHNOLOGY · PI KANG-MIELER, JENNIFER J · 2019 to 2023
$2.7M
NEI NIH HHS P30 EY012576NEI NIH HHS R01 EY029298NEI NIH HHS R01 EY033733NEI NIH HHS U24 EY029904NIH HHS P51 OD011107
6 · The paper itself

Abstract

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.

Indexed as

Biocompatible MaterialsDrug Delivery SystemsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsAnimalsElectroretinographyFemaleFluorescein AngiographyHydrogelsIntraocular PressureIntravitreal InjectionsMacaca mulattaMaleMicrospheresPolyethylene GlycolsRetinaafliberceptBiocompatible MaterialsHydrogelsPolyethylene GlycolsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion Proteinsafliberceptanti-VEGFcontrolled drug deliveryintravitreal injectionnonhuman primatethermo-responsive hydrogel

Identifiers

PMID40038090
PMCPMC11884103

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.