Novel needle for intravitreal injections does not affect biological activity of anti-VEGF drugs
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https://doi.org/10.22029/jlupub-21214Abstract
Purpose: In this in vitro study, we investigated if the biological activity of commonly used VEGF antagonists might be affected by their passage through a newly designed 30 G needle (NDN) for intravitreal injection (IVI). To reduce the risk of intraocular inflammation compared to conventional injection with a standard hypodermic 30 G needle (SHN), the NDN contains an occluded front orifice and a side port for drug delivery, resulting in an altered direction of the injection stream. Methods: Anti-VEGF drugs, such as ranibizumab, faricimab, and aflibercept, were passed twice through one of the two needle types to imitate IVI. To evaluate the VEGF-A-binding capacity of the un- or pretreated antagonists, VEGF-A165 was incubated with a 1–10fold molar excess of them for 15 min at 37°C, and unbound VEGF-A was determined by ELISA. As the capture antibody and antagonists bind to the same region of the growth factor, only the non-complexed VEGF-A was measured. Biological activity of pretreated antagonists was studied by assessing their capacity to prevent VEGF-A165-induced impairment of the barrier formed by retinal endothelial cells: VEGF-A165 plus antagonists were added to the cells and, as a measure of permeability, the cell index was continuously monitored by electric cell-substrate impedance measurements for three days. Results: Only a marginal amount of free VEGF-A, if any, was detected after incubation of the growth factor with a fourfold molar excess of any of the antagonists, independent of the drugs’ pretreatment. VEGF-A165-induced low cell index values, indicative of a dysfunctional barrier, were similarly prevented by different pretreated antagonists. Conclusion: The passage of the proteins through NDN or SHN did neither affect efficient binding to their target, nor their capacity to prevent VEGF-A165-induced barrier dysfunction. Overall, regarding the stability of therapeutic proteins, the NDN was not inferior to the SHN, and can now be considered for evaluation in clinical studies.Link to publications or other datasets
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Clinical ophthalmology 19 (2025), 4233 - 4243