Novel injectable PLGA-PEG-PLGA self-assembled hydrogels for the extended and controlled release of DNA nanocarriers to prevent secondary cataracts

Cataracts are the second leading cause of blindness worldwide. There are over 20 million cataract surgeries each year, and these cases are expected to double within the next ten years. Over 40% of adults and nearly all children develop secondary cataracts, or posterior capsule opacification (PCO), following cataract surgery. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser therapy is not available worldwide and treatment may have adverse effects on surrounding ocular tissues. Thus, there is a considerable unmet need for more efficacious and convenient treatments to prevent PCO. Injectable, stimuli-responsive gels were designed using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)) triblock copolymer and poly(L-Lysine). Hydrogel formulations with lactic acid to glycolic acid ratio of 15/1, at compositions between 14 and 25% (w/v), PLGA/PEG ratio of 2/1, and PLL concentrations between 10 and 40% (w/v) allowed for over 90% light transmittance, gel formation at 35°C, and controlled release of 3DNA® nanocarriers loaded with doxorubicin with the G8 monoclonal antibody conjugated (3DNA®:DOX:G8) for over four weeks. The physical and morphological states of this novel, thermo-sensitive hydrogel can be easily tailored for the purpose of modulating drug delivery utilizing nucleic acids. This technology offers a more effective and efficient method of ocular therapy by providing controlled delivery of 3DNA conjugates designed to specifically target cells that cause PCO. Our US patent pending technology has high potential as a more efficacious delivery method for a wide range of other therapeutics to treat a number of ocular diseases.