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Sarah Molokhia, Randon M Burr, Maggie Flood, Moritz Vallrath, Gerhard Winter, Balamurali Krishna Ambati; Lens Capsule Biodegradable Lipid Implant for Sustained-Release Anti-VEGF Therapy of Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4004. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
a) to manufacture aseptic Lipid Lucentis Implants (LLI) for in vivo use, b) to study the LLI in vitro drug release over 14 weeks
Lucentis was dialyzed with a dialysis tube specification of MWCO 3500 Da using 50 mM sodium phosphate buffer pH 6.2 at 4°C under stirring for 24 hrs. The formulation was then freeze dried and monomer content and main peak area were measured to examine the stability of Lucentis by size exclusion chromatography and hydrophobic interaction chromatography. Lipid blend were then extruded with defined settings and dimensions. Gamma-irradiation was used as sterilization method for raw lipid and an aseptic manufacturing of implants was performed. The extruded lipid strand was shaped in a semi-circle manner using a glass rod with an inner diameter of 9.4 mm (Fig.1). For the in vitro release kinetics studies, the LLI implants with 5.0% protein load were placed into vials with 2.0 ml of isotonic 0.01 M phosphate buffer pH 7.4 containing 0.05% (w/v) sodium azide. The vials were placed in a horizontal shaker and at predetermined time points the release medium was completely exchanged and the amounts of Lucentis were determined by size-exclusion chromatography.
The LLI implant weight was approximately 35 mg. The LLI showed good colloidal stability (no loss of monomeric form during incubation over 98 days). Fig 2. shows sustained release of Lucentis over 14 weeks (~100 days). The rate of release of Lucentis from the LLI after day 10 was approximately 10.3 µg/day.
No commercial ocular sustained release implant for anti-VEGF exists today. The LLI technology, which uses a biodegradable, biocompatible and sustained drug delivery lipid platform, would provide a significant breakthrough in sustained release anti-VEGF and protein molecules. The novel approach of using a Lipid matrix for ocular sustained release delivery and preserving protein stability is very promising. The implant procedure could be performed by a general ophthalmologist and not necessarily a vitreoretinal surgeon, reducing cost and increasing availability.
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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