Hana S. Alhamadsheh, Roshanak Rahimian, Miki Park, Mamoun M. Alhamadsheh, Hala Aldawod
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引用次数: 0
Abstract
Effective opioid management in neonatal abstinence syndrome (NAS) and opioid use disorder (OUD) requires maintaining low, stable plasma opioid levels to prevent withdrawal without central side effects. Current treatments rely on frequent opioid dosing, such as oral morphine every few hours for up to 3 weeks in NAS, leading to plasma level fluctuations and increased risk of toxicity or withdrawal. Herein, the design and characterization of AG10-L-E2-morphine, a prodrug that forms a zwitterionic subcutaneous depot for sustained morphine release is reported. In rats, a single subcutaneous dose of AG10-L-E2-morphine maintained plasma morphine levels for over 72 h without inducing respiratory depression, even at high doses. The prodrug is stable in human plasma and specifically activated by liver carboxylesterase enzyme 2 (CES2), supporting its safety and translational potential. This long-acting system could improve NAS care by enabling convenient dosing and early integration of nonpharmacologic strategies, ultimately reducing hospital stays and healthcare burden.
期刊介绍:
Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
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