title: Novel organic salts based on fluoroquinolone drugs: synthesis, bioavailability and toxicological profiles.
abstract: In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), novel organic salts containing fluoroquinolones (e.g. ciprofloxacin and norfloxacin) were prepared, using an optimized synthetic procedure based on direct protonation, with different biocompatible counter ions such as mesylate, gluconate and glycolate. All the prepared organic salts were characterized by spectroscopic techniques, mass spectrometry and thermal analysis. Solubility studies in water and simulated biological fluids at 25°C and 37°C were also performed. Additionally, octanol-water and phospholipid-water partition coefficients were measured at 25°C. The cytotoxicity and anti-inflammatory efficacy using an human cell model of intestinal epithelia (Caco-2 cells) were also evaluated and compared to those of the parent APIs. The adequate selection of the biocompatible anions allows the tuning of important physical, thermal and toxicological properties.
authors.affiliation: Instituto de Tecnologia Química e Biológica,(1) Universidade Nova de Lisboa, Avenida da República, Estação Agronómica Nacional, Oeiras, 2780-157, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Florindo
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Caparica, 2829-516, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Costa
authors.affiliation: Grupo de Investigação em Bioengenharia e Química Biofarmacêutica, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto 4200-150, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Matos
authors.affiliation: Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2781-901, Portugal.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Nunes
authors.affiliation: Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2781-901, Portugal.
authors.forename: Ana N
authors.initials: AN
authors.lastname: Matias
authors.affiliation: Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2781-901, Portugal.
authors.forename: Catarina M M
authors.initials: CM
authors.lastname: Duarte
authors.affiliation: Instituto de Tecnologia Química e Biológica,(1) Universidade Nova de Lisboa, Avenida da República, Estação Agronómica Nacional, Oeiras, 2780-157, Portugal.
authors.forename: Luís Paulo N
authors.initials: LP
authors.lastname: Rebelo
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Caparica, 2829-516, Portugal. Electronic address: lbranco@fct.unl.pt.
authors.forename: Luís C
authors.initials: LC
authors.lastname: Branco
authors.affiliation: Instituto de Tecnologia Química e Biológica,(1) Universidade Nova de Lisboa, Avenida da República, Estação Agronómica Nacional, Oeiras, 2780-157, Portugal. Electronic address: imarrucho@itqb.unl.pt.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Marrucho
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D001682:Biological Availability; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D005942:Gluconates / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D006016:Glycolates / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008698:Mesylates / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D008823:Micelles; D009643:Norfloxacin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D005942:Gluconates; D006016:Glycolates; D008698:Mesylates; D008823:Micelles; D012997:Solvents; D014867:Water; D010767:Phosphorylcholine; C039128:miltefosine; D002939:Ciprofloxacin; D009643:Norfloxacin
keywords: Bioavailability; Cytotoxicity; Fluoroquinolones; Ionic liquids; Solubility