US researchers have developed a proliferative retinopathy treatment that could offer a less-invasive alternative to intravitreal injections (IVI) for diabetic retinopathy, retinopathy of prematurity and neovascular age-related macular degeneration.
Writing in Theranostics, the Wayne State University and Washington State University team said their trehalose-dendrimer (tre-d) nanocarrier, loaded with axitinib (Inlyta, an oral tyrosine kinase inhibitor used to treat advanced renal cell carcinoma), selectively localised to aberrant neovascular tufts after systemic administration in a mouse model. Corresponding author Dr Nikhlesh Singh said the platform could potentially eliminate the need for painful IVI.
In the preclinical study, a single intraperitoneal injection of tre-d-axitinib significantly reduced retinal neovascularisation, tuft formation and vessel anastomoses compared with controls. In human retinal microvascular endothelial cells, the nanocarrier also inhibited VEGFA-induced proliferation, migration, sprouting and tube formation, said authors.
The nanocarrier showed minimal off-target uptake, with less than 1% accumulation in major organs apart from the kidneys, at around 5%, alongside rapid renal clearance and no significant liver or kidney toxicity, said researchers. However, tre-d-axitinib also increased vaso-obliteration in the ischaemic retina, which they said needs further investigation.
Several authors reported pending patents and invention disclosures related to the platform.
