By exploiting long chain non-covalent interactions using a biomimetic strategy, we have synthesized and characterized a novel platform of optically clear, self-assembling gels for sustained release of drug-containing, nucleic acid (NA) nanoconjugates for ocular drug delivery to the anterior and posterior segments of the eye. Gels contain polycations and polyanions of varying molecular weight with poly(D,L-lactic-co-glycolic acid)-b- poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers. For the first time, release has been shown to be finely controlled by number and type of non-covalent interactions leading to release durations over 5 months compared to only 28 day release provided by unmodified gels. Additional gel properties such as the lactic acid (LA) to glycolic acid (GA) ratio, the PLGA/PEG ratio, polymer solution composition, and homopolymer MW and concentration were varied.
Formulations have been tested both in-vitro and in-vivo with groundbreaking results for the prevention of fibrotic ocular diseases such as posterior capsular opacification (PCO) and proliferative vitreoretinopathy (PVR). Extended release of NA nanocarriers specifically targeted and depleted myofibroblasts and their progenitors with greater success than a bolus dose of nanocarriers, preventing PCO and PVR formation with minimal off-target effects. Our findings suggest that extended delivery of these DNA-based nanocarriers can have therapeutically relevant effects in the prevention of PCO and PVR. Moreover, the versatility of this novel gel formulation allows it to be modified to deliver different therapeutic agents and treat a wide array of ocular diseases.
By utilizing new biomaterials, more efficient and efficacious treatment of ocular disease is on the horizon with strong potential to lead to better patient outcomes for preventable and untreated disease.