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Ben Michael Davis, Eduardo Maria Normando, Li Guo, Paul OShea, Stephen E Moss, Satyanarayana Somavarapu, M Francesca Cordeiro; Topical Delivery of Avastin to the Posterior Segment of the Eye in vivo using Annexin A5-associated Liposomes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):450. doi: https://doi.org/.
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Intraocular injection is presently the only route of administration for large protein therapeutics, including the anti-Vascular Endothelial Growth Factors Lucentis (ranibizumab) and Avastin (bevacizumab). Anti-VEGFs have revolutionised the management of age-related macular degeneration and have increasing indications for use as sight-saving therapies in diabetes and retinal vascular disease. The present study investigates whether the anionic phospholipid binding protein annexin A5 (Anx5) may aid the delivery of liposome encapsulated anti-VEGFs to the posterior ocular tissues after topical instillation.
Several different in vitro assays were used to investigate the uptake and transcytosis of different liposomal drug carrier systems across corneal (HCE-S) epithelial barrier models. From this a novel liposomal formulation was developed comprising Anx5, phosphatidylcholine, phosphatidylserine, cholesterol and α-tocopherol and encapsulating Avastin using the lipid-film hydration technique and characterized using FPLC, dynamic light scattering and electron microscopy. This formulation was next assessed in vivo with topical administration in rat and rabbit eyes, with quantification of the Avastin concentration in the posterior segment tissues by ELISA.
The presence of annexin A5 was found to significantly (p<0.05) increase HCE-S uptake and transcytosis. Similarly Anx5 was found to significantly increase the concentration of liposome encapsulated avastin detected in the posterior of the rat eye (127 ng/g versus 26 ng/g) and rabbit retina (18 ng/g versus 1 ng/g) in vivo after topical application, compared to equivalent instillation in the absence of annexin A5.
Anx5-associated liposomes appears to be promising method for topical drug delivery to the back of the eye. Increasing indications for anti-VEGF therapies have put an unprecedented strain on the healthcare system, where often there are insufficient ophthalmologists or trained assistants to provide the frequency of administration and standard of care recommended. Less invasive interventions are therefore needed. This study demonstrates that topical delivery of avastin can be achieved using annexin A5 associated liposomes, and provides strong evidence that anti-VEGF eye-drops could be the treatment of choice where chronic therapy is indicated.
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