TY - JOUR
T1 - Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery
AU - Hsueh, Henry T.
AU - Chou, Renee Ti
AU - Rai, Usha
AU - Liyanage, Wathsala
AU - Kim, Yoo Chun
AU - Appell, Matthew B.
AU - Pejavar, Jahnavi
AU - Leo, Kirby T.
AU - Davison, Charlotte
AU - Kolodziejski, Patricia
AU - Mozzer, Ann
AU - Kwon, Hye Young
AU - Sista, Maanasa
AU - Anders, Nicole M.
AU - Hemingway, Avelina
AU - Rompicharla, Sri Vishnu Kiran
AU - Edwards, Malia
AU - Pitha, Ian
AU - Hanes, Justin
AU - Cummings, Michael P.
AU - Ensign, Laura M.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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 develop 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) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~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.
AB - 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 develop 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) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~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.
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U2 - 10.1038/s41467-023-38056-w
DO - 10.1038/s41467-023-38056-w
M3 - Article
C2 - 37130851
AN - SCOPUS:85157970811
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2509
ER -