We have the retina to thank for the gift of sight—the thin tapestry of light-sensitive cells and nerves at the back of the eye captures light and transforms it into the vivid imagery of our visual world. However, retinal neovascular diseases such as diabetic retinopathy disrupt this; poor blood flow triggers the abnormal growth of blood vessels in the retina which lead to vision loss.
The complex anatomy of the eye creates a tricky drug delivery challenge—current treatments for retinal conditions usually require invasive intravitreal injections to access the affected tissues. Going to the clinic for these injections can be a hassle, and may be associated with sight-threatening complications.
“Topical drugs can revolutionise the treatment paradigm of retinal diseases,” commented Xinyi Su, Acting Executive Director at A*STAR’s Institute of Molecular and Cell Biology (IMCB). Su’s team has been pioneering a polymer-based delivery system for administering medications that counteract abnormal vascular growth in the retina.
In partnership with Xian Jun Loh, Executive Director at A*STAR’s Institute of Materials Research and Engineering (IMRE), the researchers adopted a nanomicelle (nEPC) approach—tiny drug-bearing vessels designed to traverse corneal barriers to reach the retina.
Together with researchers from the National University Hospital, National University of Singapore, Singapore Eye Research Institute and the Singapore University of Technology and Design, Su’s team loaded nEPCs with an antiangiogenic agent, aflibercept, and tested the nanomicelles’ potency in experimental eye models.
Microscopic images of nEPC’s action in eye cell and tissue models. (a) nEPCs loaded with aflibercept (red) visibly penetrate a mouse cornea when applied topically to the epidermal layer. (b) nEPCs inhibit the formation of vascular structures (green outlines with blue nuclei) on a 3D cell culture chip of human vascular endothelial cells.
The nanomicelles proved adept at ferrying aflibercept to the retina and enhancing drug concentrations in the affected tissues, thwarting the formation of blood vessels and mitigating vessel leakage in mice models of retinal disease.
Promisingly, the nanomicelle system showed biocompatibility with human cell line models, suggesting a less invasive and promising alternative to current treatments.
Su emphasised that the unique polymer used in the nanomicelle formulation may have intrinsic properties to suppress vascular proliferation or growth—biological processes implicated in retinal disorders.
"We hypothesise that these anti-antiangiogenic effects may be derived from the inhibition of vascular endothelial proliferation—a key part aspect of angiogenesis,” explained Su, adding that the team plans to investigate these pathways in future studies.
For now, the team is accelerating the commercialisation efforts of their new technology with a new venture, Vitreogel Innovations, to advance the nEPC polymer towards clinical applications.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB) and the Institute of Materials Research and Engineering (IMRE).
