Synthesis and characterization of an injectable telechelic material for the epiretinal delivery of retinal gene therapies

Abstract

There is a need to develop safer, more efficient, and targeted strategies for the delivery of retinal gene therapies. Current strategies may require high dose therapeutics administered intravitreally or complex subretinal surgical delivery with increased risks. An optimized material carrier could enable localized delivery of therapeutics without extensive surgery. Here, we report a novel material carrier formed by octadecane-poly(ethylene glycol)-octadecane (OPO) molecules. OPO molecules were synthesized via a Williamson reaction. In aqueous solution, the octadecane heads associate to form a telechelic network. We extensively characterized this material using a variety of rheological and spectroscopic techniques. At both room temperature and body temperature, the material is a viscoelastic fluid that exhibits Maxwellian behavior. It is transparent, injectable, and spreadable without fragmentation. Delivery agents can be facilely loaded into the material as the OPO network forms. In bulk solution, the network dissolves, releasing loaded agents over a period of ∼60 min. Placement of an unloaded backing layer next to a loaded layer promotes release from the network in a targeted direction. We additionally prepared OPO loaded with adeno-associated viruses (AAVs) and demonstrated that AAV titre is homogeneously distributed throughout the material, is stable for up to 3 days, and that AAVs administered in OPO are able to transduce ARPE-19 cells. We hypothesize these properties well-position OPO as an efficient carrier to deliver retinal gene therapies, and in particular AAV vectors, in vivo and may prove useful in other delivery applications. This is the first report of an injectable material that can be facilely loaded with retinal gene therapies. The results presented here are a crucial preliminary step in advancing a materials-based strategy for administering gene therapies to the retina.