Extended Release of Doxorubicin-Loaded 3DNA Nanocarriers fromIn-SituForming, Self-Assembled Hydrogels

Abstract

Purpose: Cataracts are the leading cause of blindness worldwide, resulting in over 30 million surgeries each year. These cases are expected to double within the next 10 years. About 25% of all patients develop secondary cataracts or posterior capsule opacification (PCO) postsurgery. PCO is a vision impairment disorder that develops from myofibroblasts migration and contraction that deforms the capsule surrounding the lens. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser is not available worldwide and adverse side effects may arise. Thus, there is a considerable unmet need for more efficacious and convenient preventive treatments for PCO. Our work focuses on engineering an innovative, prophylactic sustained release platform for DNA-based nanocarriers to further reduce the incidence of PCO. Methods: Novel, optically clear, self-assembled poly(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) triblock copolymer hydrogels were used for the sustained release of the DNA-based nanocarriers (3DNA Ò) loaded with cytotoxic doxorubicin (DOX) and targeted with a monoclonal antibody called G8 (3DNA:DOX:G8), which is specific to cells responsible for PCO. Results: The 29 (w/v)% polymer hydrogels with the 3DNA nanocarriers presented over 80% of light transmittance, soft mechanical properties (<350 Pa), and sustained release for 1 month. Conclusions: In this work, we show for the first time that the hydrophobic PLGA-PEG-PLGA hydrogels can be used as platforms for sustained delivery of nucleic acid-based nanocarriers. This work demonstrates that polymeric formulations can be used for the extended delivery of ocular therapeutics and other macromolecules to treat a variety of ocular conditions.