abstract
The critical scenario of antimicrobial resistance to antibiotics highlights the need for improved therapeutics and/ or formulations. Herein, we demonstrate that deep eutectic solvents (DES) formulations are very promising to remarkably improve the solubility, stability and therapeutic efficacy of antibiotics, such as ciprofloxacin. DES aqueous solutions enhance the solubility of ciprofloxacin up to 430-fold while extending the antibiotic stability. The developed formulations can improve, by 2 to 4-fold, the susceptibility of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria to the antibiotic. They also improve the therapeutic efficacy at concentrations where bacteria present resistance, without promoting tolerance development to ciprofloxacin. Furthermore, the incorporation of DES decreases the toxicity of ciprofloxacin towards immortalized human epidermal keratinocytes (HaCat cells). The results herein reveal the pioneering use of DES in fluoroquinolone-based formulations and their impact on the antibiotic's characteristics and on its therapeutic action.
keywords
PSEUDOMONAS-AERUGINOSA; MULTIDRUG-RESISTANCE; HYDROCHLORIDE FORMS; TOPOISOMERASE-II; EFFLUX PUMPS; CIPROFLOXACIN; SOLUBILITY; QUINOLONE; MEROPENEM; TETRACYCLINE
subject category
Pharmacology & Pharmacy
authors
Pedro, SN; Gomes, ATPC; Oskoei, P; Oliveira, H; Almeida, A; Freire, MG; Silvestre, AJD; Freire, CSR
our authors
Armando Jorge Domingues Silvestre
Full professor
Carmen Sofia da Rocha Freire Barros
Coordinating Researcher
Helena Oliveira
Post-Doc Fellowship
Mara Guadalupe Freire Martins
Coordinating Researcher
Párástu Mariana Baghaei Oskoei
PhD Student
Sónia Isabel Neto Pedro
PhD StudentGroups
G1 - Porous Materials and Nanosystems
G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials
acknowledgements
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, and CESAM, UID/AMB/50017/2019 & UIDB/50017/2020, LA/P/0094/2020 , financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. S. N. Pedro acknowledges the PhD grant SFRH/BD/132584/2017 and P. Oskoei for the PhD grant BD/REIT/8623/2020. H. Oliveira thanks FCT for the research contract under Scientific Employment Stimulus (CEEC-IND/04050/2017) .