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dc.contributor.author
Braga, Monica Andrea
dc.contributor.author
Martini, María Florencia
dc.contributor.author
Pickholz, Mónica Andrea
dc.contributor.author
Yokaichiya, F.
dc.contributor.author
Franco, M. K. D.
dc.contributor.author
Cabeça, L. F.
dc.contributor.author
Guilherme, V. A.
dc.contributor.author
Silva, C. M. G.
dc.contributor.author
Limia, C. E. G.
dc.contributor.author
de Paula, Eneida
dc.date.available
2018-03-16T15:44:57Z
dc.date.issued
2016-02
dc.identifier.citation
Braga, Monica Andrea; Martini, María Florencia; Pickholz, Mónica Andrea; Yokaichiya, F.; Franco, M. K. D.; et al.; Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia; Elsevier Science; Journal of Pharmaceutical and Biomedical Analysis; 119; 2-2016; 27-36
dc.identifier.issn
0731-7085
dc.identifier.uri
http://hdl.handle.net/11336/39076
dc.description.abstract
Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics. In this work, we describe the preparation and characterization of an inclusion complex of clonidine in hydroxypropyl-beta-cyclodextrin (HP-β-CD), as revealed by experimental (UV-vis absorption, SEM, X-ray diffraction, DOSY- and ROESY-NMR) and theoretical (molecular dynamics) approaches. CND was found to bind to HP-β-CD (Ka=20M-1) in 1:1 stoichiometry. X-ray diffractograms and SEM images provided evidence of inclusion complex formation, which was associated with changes in the diffraction patterns of the pure compounds. NMR experiments revealed changes in the chemical shift of H3HP-β-CD hydrogens (δ=0.026ppm) that were compatible with the insertion of CND in the hydrophobic cavity of the cyclodextrin. Molecular dynamics simulation with the three CND species that exist at pH 7.4 revealed the formation of intermolecular hydrogen bonds, especially for the neutral imino form of CND, which favored its insertion in the HP-β-CD cavity. In vitro assays revealed that complexation retarded drug diffusion without changing the intrinsic toxicity of clonidine, while in vivo tests in rats showed enhanced sensory blockade after the administration of 0.15% CND, with the effect decreasing in the order: CND:HP-β-CD+bupivacaine>CND+bupivacaine>bupivacaine>CND:HP-β-CD>clonidine. The findings demonstrated the suitability of the complex for use as a drug delivery system for clinical use in antinociceptive procedures, in association with local anesthetics.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Clonidine
dc.subject
Cyclodextrin
dc.subject
Drug Delivery
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Magnetic Resonance
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Molecular Dynamics
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-14T17:07:26Z
dc.journal.volume
119
dc.journal.pagination
27-36
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Braga, Monica Andrea. Universidade Estadual de Campinas; Brasil
dc.description.fil
Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
dc.description.fil
Fil: Yokaichiya, F.. Comissão Nacional de Energia Nuclear. Instituto de Pesquisas Energéticas e Nucleares; Brasil. Universidade de Sao Paulo; Brasil. Helmholtz-Zentrum. Department of Quantum Phenomena in Novel Materials; Alemania
dc.description.fil
Fil: Franco, M. K. D.. Comissão Nacional de Energia Nuclear. Instituto de Pesquisas Energéticas e Nucleares; Brasil. Universidade de Sao Paulo; Brasil
dc.description.fil
Fil: Cabeça, L. F.. Universidade Federal do Paraná; Brasil
dc.description.fil
Fil: Guilherme, V. A.. Universidade Estadual de Campinas; Brasil
dc.description.fil
Fil: Silva, C. M. G.. Universidade Estadual de Campinas; Brasil
dc.description.fil
Fil: Limia, C. E. G.. Universidade Estadual de Campinas; Brasil
dc.description.fil
Fil: de Paula, Eneida. Universidade Estadual de Campinas; Brasil
dc.journal.title
Journal of Pharmaceutical and Biomedical Analysis
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jpba.2015.11.015
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0731708515302363


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