Ex vivo model for the measurement of intraocular pressure and force of injection during the administration of hollow microneedles in porcine sclera

Abstract

AbstractPurpose: The current gold standard treatment option for posterior segment diseases such as age‐related macular degeneration is the delivery of drug into the vitreous cavity by intravitreal injection. This method is, however, associated with several issues including low patient compliance and the risk of adverse effects [1]. Microneedles (MNs), designed to deliver their payload into the sclera, offer a minimally invasive means of providing localized drug delivery to the eye, providing a potentially more patient‐friendly alternative. MNs for ocular drug delivery have gained significant interest in recent years; however, for clinical acceptability, safe values for parameters such the injection force and changes in intraocular pressure (IOP) are critical. This work investigated the effects that changing MN design parameters (e.g., bevel angle, needle length and needle gauge) had on both the force of penetration (FoP) and depth of penetration (DoP) achieved in ex vivo porcine sclera at clinically relevant locations. The model used a pressure transducer to allow for real‐time monitoring of IOP over the injection procedure.Methods: Stainless steel hollow microneedles (ssHMNs) were fabricated from conventional hypodermic needles, with a range of bevel angles (30–75°) cut in triplicate using Wire Electrical Discharge Machining. Needle heights were adjusted as required using 3D‐printed adapters. To assess FoP and DoP, ssHMNs were inserted into ex vivo porcine sclera with images being captured using optical coherence topography. IOP changes during the injection procedure were monitored in real‐time using a pressure transducer.Results: ssHMNs were shown to partially penetrate the ex vivo porcine sclera. Average values obtained for FoP and DoP were shown to be dependent on sclera location. Peak IOP values were observed upon scleral penetration, with these being lower with smaller needle sizes. Similarly, average FoP values were found to decrease for higher gauge needles and smaller bevel angles.Conclusions: This work demonstrates the effects of changing design parameters of ssHMNs on the FoP and DOP achieved in ex vivo porcine sclera, as well as changes in IOP.Reference1. “Stimuli sensitive ocular drug delivery systems,” in Drug Targeting and Stimuli Sensitive Drug Delivery Systems, 2018, pp. 211–270.