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Naa Dei Nikoi, Thomas Lovatt, Anna F.A. Peacock, Felicity de Cogan; Membrane Penetrating Poly Amines as Non-Invasive Drug Delivery Vehicles for anti-VEGF Therapies to Treat Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2904.
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To investigate the efficacy of non-invasive delivery of bevacizumab to the posterior segment of the eye using membrane penetrating polyamines (MPPA).Age-related macular degeneration (AMD) is a leading cause of vision loss in Europe and the US. Current therapy for neovascular AMD consists of monthly intravitreal injections of anti-VEGF antibodies for a minimum of 5 years. For most patients, it is an effective therapy. However, it has significant side effects, including uveitis, retinal detachment, and raised intraocular pressure.There is an unmet need for topical applications that the patient can apply themselves. However, the eye poses significant difficulties to drug delivery as the structures of the eye act as barriers to the penetration of drugs. The MPPA is a novel system which will allow the anti-VEGF therapies to be applied topically instead of intravitreal injection.
Initial transmembrane experiments showed that the MPPAs could deliver bevacizumab across a membrane. Subsequently, MPPA molecules were used to deliver anti-VEGF therapeutic bevacizumab to the posterior segment of a porcine eye ex vivo. The eyes were randomly assigned a group to control, MPPA, MPPA+bevacizumab or bevacizumab alone. Bevacizumab was mixed with MPPA and then applied topically to the front of the porcine eye. Each eye had a 50 µL drop applied to the ocular surface. The eyes were incubated for 40 minutes in a humidified chamber, and the levels of bevacizumab in each tissue were measured using ELISA.
In transmembrane experiments, MPPAs were able to deliver 30% of the protein across the membrane within 60 seconds of application. In porcine eyes, the MPPA+bevacizumab eye drops delivered 10±9 µg /mL for MPPA and 1.5 ± 0.9 µg /mL to the retina, all significantly higher levels (p=0.004) than MPPA, saline, or bevacizumab alone (<0.007 µg). Additionally, the amount of bevacizumab delivered was significantly higher than that delivered using the polyarginine CPP reported earlier by de Cogan et al. IOVS 2017.
MPPAs are promising agents for drug delivery, being able to deliver bevacizumab both across membranes and to the posterior segment of the eye ex vivo in porcine eyes.
This is a 2020 ARVO Annual Meeting abstract.
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