Biology Research Works
Permanent URI for this collectionhttp://hdl.handle.net/1903/13
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Item Supplementary materials for machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery(2023) Chou, Renee Ti; Hsueh, Henry T.; Rai, Usha; Liyanage, Wathsala; Kim, Yoo Chun; Appell, Matthew B.; Pejavar, Jahnavi; Leo, Kirby T.; Davison, Charlotte; Kolodziejski, Patricia; Mozzer, Ann; Kwon, HyeYoung; Sista, Maanasa; Anders, Nicole M.; Hemingway, Avelina; Rompicharla, Sri Vishnu Kiran; Edwards, Malia; Pitha, Ian; Hanes, Justin; Cummings, Michael P.; Ensign, Laura M.; Cummings, Michael P.; Ensign, Laura M.Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We developed a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) was conjugated to brimonidine, an intraocular pressure (IOP)-lowering drug that is prescribed for three times per day topical dosing, IOP reduction was observed for up to 18 days after a single intracameral HR97-brimonidine injection in rabbits. Further, the cumulative IOP-lowering effect was increased ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.