resumo
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.
palavras-chave
PSEUDOMONAS-AERUGINOSA; MULTIDRUG-RESISTANCE; HYDROCHLORIDE FORMS; TOPOISOMERASE-II; EFFLUX PUMPS; CIPROFLOXACIN; SOLUBILITY; QUINOLONE; MEROPENEM; TETRACYCLINE
categoria
Pharmacology & Pharmacy
autores
Pedro, SN; Gomes, ATPC; Oskoei, P; Oliveira, H; Almeida, A; Freire, MG; Silvestre, AJD; Freire, CSR
nossos autores
Armando Jorge Domingues Silvestre
Professor Catedrático
Carmen Sofia da Rocha Freire Barros
Investigador Coordenador
Helena Oliveira
Bolseiro de pós-Doutoramento
Mara Guadalupe Freire Martins
Investigador Coordenador
Párástu Mariana Baghaei Oskoei
Estudante de doutoramento
Sónia Isabel Neto Pedro
Estudante de doutoramentoGrupos
G1 - Materiais Porosos e Nanossistemas
G4 - Materiais Renováveis e Economia Circular
G5 - Materiais Biomiméticos, Biológicos e Vivos
agradecimentos
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) .