From ascorbic acid to N-acetylcysteine: self-assembled clarithromycin liquid crystals as a new generation of carrier-free antibiotics.

Antimicrobial resistance demands innovative molecular strategies to enhance antibiotic efficacy while minimizing the use of excipients. Building on the previously reported clarithromycin: ascorbic acid cholesteric liquid crystal, we present a new carrier-free system formed via the self-assembly of clarithromycin and N-acetylcysteine, capable of forming both a cholesteric liquid crystal and its corresponding xerogel. The system exhibited intense birefringence and characteristic optical textures, confirming the formation of an ordered mesophase sensitive to temperature and N-acetylcysteine concentration. Rheological studies revealed viscoelastic solid-like behaviour, while powder X-ray diffraction and scanning electron microscopy of the xerogel evidenced a lamellar organization with an enhanced degree of crystalline order. Fourier transform infrared spectroscopy and nuclear magnetic resonance studies indicated the formation of a new salt stabilized through ionic interactions and hydrogen bonding. The cholesteric liquid crystal enhanced the antimicrobial and antibiofilm activity of clarithromycin against Staphylococcus aureus and, together with the mucolytic properties of N-acetylcysteine, positions it as a promising candidate for application in cystic fibrosis. These results establish self-assembled clarithromycin liquid crystals as a new generation of carrier-free antibiotics.