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Alexander T Nguyen, Laurel T Tainsh, Patrick Coady, Maryam Ghiassi, Lawrence J Rizzolo, Ron A Adelman; Factors affecting protein aggregation for bevacizumab. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4003.
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© ARVO (1962-2015); The Authors (2016-present)
Silicone oil microdroplets following intravitreal injections have gained increased recognition but their clinical significance remains unclear. It has been hypothesized, though, that small quantities of silicone oil may play a role in the long-term increases in intraocular pressure (IOP) following intravitreal injections of bevacizumab. Postulated mechanisms include obstruction of trabecular meshwork by silicone oil and/or large protein aggregates. The silicone oil microdroplets are presumed to originate from the needle syringes used for injection. Our investigation aims to characterize some determinants of aggregation for bevacizumab that may be relevant in the clinical setting of intravitreal injections.
In samples of bevacizumab, the effects of needle syringe design and agitation on aggregate formation were evaluated. Needle syringes lubricated with silicone oil (Becton and Dickinson, 1 mL tuberculin syringe) were compared with needle syringes designed to minimize drug contact with silicone oil (West Pharmaceuticals, D21-7H 1 mL syringe). Aggregation associated with needle syringe drug delivery was evaluated with comparison to direct micropipette transfer without a needle syringe vehicle. To estimate aggregation, prepared samples were centrifuged and then analyzed by spectrophotometry (Nanodrop Lite, Thermo Fisher Scientific, Inc.) at 280 nm (OD280).
Drug transfer of bevacizumab by a tuberculin syringe resulted in a lower OD280 after centrifugation than direct micropipette transfer (t-test, p<0.0005). Agitating a vial of bevacizumab also yielded a lower OD280 (t-test, p<0.0032). The OD280 was similar for both tuberculin syringes (7.02±4.29) and D21-7H syringes (7.14±1.62).
For bevacizumab, agitation and drug transfer with needle syringes is associated with increased protein aggregation when compared to direct micropipette transfer. Further studies can help characterize factors affecting protein aggregation from needle syringe drug delivery.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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