April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Topical Delivery of Avastin to the Posterior Segment of the Eye in vivo using Annexin A5-associated Liposomes
Author Affiliations & Notes
  • Ben Michael Davis
    Visual Neuroscience, UCL, London, United Kingdom
  • Eduardo Maria Normando
    Visual Neuroscience, UCL, London, United Kingdom
  • Li Guo
    Visual Neuroscience, UCL, London, United Kingdom
  • Paul OShea
    Cell Biophysics Group, University of Nottingahm, Nottingham, United Kingdom
  • Stephen E Moss
    Cell biology, UCL, London, United Kingdom
  • Satyanarayana Somavarapu
    School of Pharmacy, UCL, London, United Kingdom
  • M Francesca Cordeiro
    Visual Neuroscience, UCL, London, United Kingdom
    Western Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships Ben Davis, None; Eduardo Normando, None; Li Guo, None; Paul OShea, None; Stephen Moss, UCL (P); Satyanarayana Somavarapu, None; M Francesca Cordeiro, UCL (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 450. doi:https://doi.org/
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 583 lipids • 608 nanomedicine • 607 nanotechnology  
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