Pharmaceutics
Oseltamivir-Based Organic Salts and Ionic Liquids: Physicochemical Properties, Cytotoxicity, and Neuraminidase Inhibition
By Madeira DA, Correia V, Santos L and 2 others.
Abstract
Background
Neuraminidase (NA) inhibitors are widely used for the treatment of influenza, but the emergence of resistance and limitations in drug formulation can compromise their therapeutic performance. This study investigated whether counterion exchange can modulate the physicochemical properties, cytotoxicity, and NA-inhibitory activity of oseltamivir (OS) while preserving its covalent structure.
Methods
Five OS-based ionic formulations, [OS][C1SO3], [OS][C3SO3], [OS][C6SO3], [OS][TolSO3], and [OS][CSA], were synthesized and characterized by NMR and ATR-FTIR spectroscopy, with isolated yields ranging from 84 to 88%. Spectroscopic data confirmed the formation of the desired 1:1 salts and showed that the OS ethyl ester remained chemically intact. The formulations were evaluated for aqueous solubility, octanol/water partitioning, cytotoxicity toward MDCK-SIAT1 cells, and NA-inhibitory activity using a MUNANA-based assay against NAs from A(H1N1)pdm09, its H275Y oseltamivir-resistant variant, A(H3N2), and type B influenza viruses.