TY - JOUR
T1 - Extended Release of Doxorubicin-Loaded 3DNA Nanocarriers from In-Situ Forming, Self-Assembled Hydrogels
AU - Osorno, Laura L.
AU - Medina, Jamie D.R.
AU - Maldonado, Daniel E.
AU - Mosley, Robert J.
AU - Byrne, Mark E.
N1 - Funding Information:
We thank Genisphere, LLC, our collaborator, for facilitating their 3DNA® nanocarriers that were specifically synthesized for this project. This work was supported by funding from the Cooper Foundation.
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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®) 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.
AB - 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®) 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.
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U2 - 10.1089/jop.2019.0145
DO - 10.1089/jop.2019.0145
M3 - Article
C2 - 32466697
AN - SCOPUS:85088850464
VL - 36
SP - 447
EP - 457
JO - Journal of Ocular Pharmacology and Therapeutics
JF - Journal of Ocular Pharmacology and Therapeutics
SN - 1080-7683
IS - 6
ER -