title: Structural and thermodynamic characterization of doxycycline/β-cyclodextrin supramolecular complex and its bacterial membrane interactions.
abstract: Doxycycline is a semi-synthetic antibiotic commonly used for the treatment of many aerobic and anaerobic bacteria. It inhibits the activity of matrix metalloproteinases (MMPs) and affects cell proliferation. In this study, the structural and thermodynamic parameters of free DOX and a DOX/βCD complex were investigated, as well as their interactions and effects on Staphylococcus aureus cells and cellular cytotoxicity. Complexation of DOX and βCD was confirmed to be an enthalpy- and entropy-driven process, and a low equilibrium constant was obtained. Treatment of S. aureus with higher concentrations of DOX or DOX/βCD resulted in an exponential decrease in S. aureus cell size, as well as a gradual neutralization of zeta potential. These thermodynamic profiles suggest that ion-pairing and hydrogen bonding interactions occur between DOX and the membrane of S. aureus. In addition, the adhesion of βCD to the cell membrane via hydrogen bonding is hypothesized to mediate a synergistic effect which accounts for the higher activity of DOX/βCD against S. aureus compared to pure DOX. Lower cytotoxicity and induction of osteoblast proliferation was also associated with DOX/βCD compared with free DOX. These promising findings demonstrate the potential for DOX/βCD to mediate antimicrobial activity at lower concentrations, and provides a strategy for the development of other antimicrobial formulations.
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Suárez
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Jessika
authors.initials: J
authors.lastname: Consuegra
authors.affiliation: Departamento de Odontologia Restauradora, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil(1).
authors.forename: Vivianne C
authors.initials: VC
authors.lastname: Trajano
authors.affiliation: Departamento de Odontologia Restauradora, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil(1).
authors.forename: Sávio M L
authors.initials: SM
authors.lastname: Gontijo
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Pedro P G
authors.initials: PP
authors.lastname: Guimarães
authors.affiliation: Departamento de Odontologia Restauradora, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil(1).
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cortés
authors.affiliation: Departamento de Farmácia, Universidade Federal de Juiz de Fora, UFJF, Campus Governador Valadares, MG. Av. Dr. Raimundo Monteiro de Rezende 330, Centro, 35010-177, Governador Valadares, MG, Brazil.
authors.forename: Ângelo L
authors.initials: ÂL
authors.lastname: Denadai
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: sinisterra@ufmg.br.
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Sinisterra
mesh_terms: D000818:Animals; D002151:Calorimetry; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004055:Differential Thermal Analysis; D004318:Doxycycline / Q000737:chemistry* / Q000494:pharmacology*; D057446:Hydrodynamics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D012542:Scattering, Radiation; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000166:cytology* / Q000187:drug effects; D055672:Static Electricity; D013816:Thermodynamics; D013818:Thermogravimetry; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D047392:beta-Cyclodextrins; C031215:betadex; D004318:Doxycycline
keywords: Antimicrobial; Cytotoxicity; Doxycycline; Membrane interactions; Susceptibility; β-Cyclodextrin