Journal
ADVANCED THERAPEUTICS
Volume 3, Issue 12, Pages -Publisher
WILEY
DOI: 10.1002/adtp.202000138
Keywords
alkali burns; corneal epithelium; diabetic corneas; EphA2; microRNA
Categories
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant [AR075049]
- NCI [CCSG P30 CA060553]
- NIH [1S10OD021704 -01]
- National Institutes of Health [EY06769, EY017539, EY019463]
- Dermatology Foundation
- Eversight research grant
- Northwestern University Post Graduate Program in Cutaneous Biology of the National Institutes of Health [T32AR060710, AR064144, AR071168]
- Prostate Cancer Foundation
- Center for Regenerative Nanomedicine (CRN)
- Nanyang Technological Institute-Northwestern University (NTU-NU) Institute for Nanomedicine
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microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. It is demonstrated that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR-HDL NPs significantly improves corneal reepithelialization following wounding compared with controls. Mouse corneas with alkali burn-induced inflammation, topically treated with HDL NPs, display clinical, morphological, and immunological improvement. These results yield a novel HDL NP-based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g., dry eye).
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