The majority of antibiotics display low oral bioavailability due to reduced solubility in water and/or inefficient permeability across biological membranes. Their efficiency is further limited by the frequent presence of polymorphic structures with different pharmaceutical activities. In this communication, we present our latest results on the development of organic salts and ionic liquids from fluoroquinolones (FQ-OSILs) as highly efficient ionic formulations of this family of antimicrobials. Ciprofloxacin and norfloxacin were used as anions and as cations, by combination with biocompatible organic counter-ions. In vitro bioavailability studies showed that all prepared FQ-OSILs presented higher solubility in water than the original drugs. All compounds were found to be isomorphic and with tailorable antimicrobial activity according to the cation–anion combination against Staphylococcus aureus, Bacillus subtilis and Klebsiella pneumoniae strains.

Graphical AbstractTackling bacterial resistance using antibiotics as ionic liquids and organic salts 2 Resistant E. coli MRSA 50 nM 5 nM Abstract: Bacterial resistance to current antibiotics has a major impact on worldwide human health, leading to 700K deaths every year. The development of novel antibiotics did not present significant progress, namely regarding clinical trials, over the last years due to low returns. Thus, innovative alternatives must be devised to tackle the continuous rise of antimicrobial resistance. Ionic Liquids and Organic Salts from Active Pharmaceutical Ingredients (API-OSILs) have risen in academia for over 10 years as an efficient formulation for drugs with low bioavailability and permeability, as well as reduction or elimination of polymorphism, thereby potentially enhancing their pharmaceutical efficiency. To the best of our knowledge, our group is the first to perform research on the development of API-OSILs from antibiotics as a way to improve their efficiency. More specifically, we have successfully combined ampicillin, penicillin and amoxicillin as anions with biocompatible organic cations such as choline, alkylpyridiniums and alkylimidazoliums.In this communication, we present our latest developments in the synthesis and physicochemical (DSC) characterization of OSILs from these antibiotics, in addition to in vitro antimicrobial activity data, in particular towards MRSA and multi-resistant E. coli, as well as sensitive strains of gram-positive and gram-negative bacteria.