Antiangiogenic nanomicelles for the topical delivery of aflibercept to treat retinal neovascular disease
Abstract
The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.
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Aflibercept-loaded nEPCs were capable of penetrating the cornea in ex vivo porcine eye models, and delivered clinically effective quantities of aflibercept to the retina in laser-induced CNV murine models.
“Researchers demonstrated that aflibercept-loaded nEPCs were capable of penetrating the cornea in ex vivo porcine eye models, and delivered a clinically effective quantities of aflibercept to the retina in the laser-induced CNV murine models.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [193]
nEPCs possess intrinsic antiangiogenic properties, which may yield synergistic outcomes in conjunction with their dual capacity to deliver anti-VEGF therapeutics.
“Notably, this research also demonstrates that nEPCs possess intrinsic antiangiogenic properties, which may yield synergistic outcomes in conjunction with their dual capacity to deliver anti-VEGF therapeutics, thereby offering a promising remedy [193].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [193]
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- Authors
- Zhao, X., Seah, I., Xue, K., Wong, W., Tan, Q. S. W., Ma, X., Lin, Q., Lim, J. Y. C., Liu, Z., Parikh, B. H., Mehta, K. N., Lai, J. W., Yang, B., Tran, K. C., Barathi, V. A., Cheong, K. H., Hunziker, W., Su, X., & Loh, X. J.
- Affiliations
- Agency for Science, Technology and Research (SG)
- National University Hospital (SG)
- Singapore University of Technology and Design (SG)
- National University of Singapore (SG)
- Corresponding author
- Su, Xinyi
- Loh, Xian Jun
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2021-12-02
- Volume
- 34
- Issue
- 25
- Pages
- e2108360-e2108360
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W3208137158
- Cited by
- 84
- References
- 48
- Citations by year
- 2026: 5 · 2025: 24 · 2024: 24 · 2023: 18 · 2022: 12 · 2021: 1
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- Agency for Science, Technology and Research (H17/01/a0/013)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- nanomicelles, aflibercept, topical drug delivery, retinal neovascular disease, choroidal neovascularization, anti-VEGF therapy, corneal penetration, polycaprolactone, polyethylene glycol, polypropylene glycol, intravitreal injection alternatives, porcine eye model, biocompatibility
- MeSH terms
- Animals, Recombinant Fusion Proteins, Retinal Diseases, Swine, Drug Delivery Systems, Choroidal Neovascularization, Angiogenesis Inhibitors, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Mice
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