Reshaping antibiotics through hydrophobic drug-bile acid ionic complexation enhances activity against Staphylococcus aureus biofilms

Publication date: 7 August 2017 Source:International Journal of Pharmaceutics, Volume 528, Issues 1–2 Author(s): Stefano Giovagnoli, Donatella Pietrella, Lanfranco Barberini, Claudio Santi, Andrea Carotti, Alessandro di Michele, Maurizio Ricci The antibiotic era is on the verge of a profound change and facing a ground shaking crisis. The frequent failures of antibiotic treatments are often associated with biofilm formation, which is responsible for chronic infections, exacerbation as well as reinfection. So far, albeit the large number of valuable strategies employed to combat biofilm formation, little success has been recorded. In this work, we propose a simple approach, based on hydrophobic ionic complexation with the bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), to enhance anti-biofilm activity of well-known antibiotics, namely kanamycin (K), amikacin (A) and vancomycin (V). Activity was evaluated against Staphylococcus aureus ATCC 29213 and six methicillin-resistant clinical isolates. The formation of a 1:4 ADCA and KDCA and 1:1 VUDCA complexes was confirmed by 1HNMR, in silico molecular dynamics simulations, as well as thermal, spectrophotometric and HPLC analyses. The complexes showed higher inhibition of S. aureus growth compared to parent drugs and a concentration-independent biofilm inhibition and dispersion capacity in the order KDCA > ADCA >>VUDCA, even at concentrations ten-fold below the MIC. S. aureus growth ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research