title: Encapsulation of Antioxidant Gallate Derivatives in Biocompatible Poly(ε-caprolactone)-b-Pluronic-b-Poly(ε-caprolactone) Micelles.
abstract: Formulation of antioxidant agents is still a challenge that limits their application in the biomedical field. Pentablock copolymers obtained through modification of two common PEO-PPO-PEO copolymers (Pluronic F127 and F68) with poly(ε-carprolactone) (PCL) were evaluated regarding their capability to form nanocarriers suitable for gallic acid, methyl gallate, and ethyl gallate. Applying a dialysis method, PCL/F127/PCL and PCL/F68/PCL self-assembled into spherical micelles in 0.9% NaCl aqueous solution but notably differed in critical micellar concentration (CMC), micelle core hydrophobicity, and micelle size, as evidenced by pyrene fluorescence, transmission electron microscopy, and dynamic light scattering. Cytotoxicity studies showed that the copolymers were safe at concentrations well above the CMC. Transfer of gallic acid and derivatives from aqueous medium to the micelle phase was characterized in terms of distribution constant and free energy of transference, which were shown to be strongly dependent on the hydrophobicity of the gallate derivatives and the length of PCL in the pentablock copolymer. Antioxidant activity of gallates was challenged against DPPH previously loaded in PCL/F127/PCL and PCL/F68/PCL micelles. The more the hydrophobicity of the gallate derivative, the greater the capability to enter in the micelle and to consume free radicals. In vitro release studies of gallic acid, methyl gallate, and ethyl gallate from the pentablock copolymer micelles also evidenced the influence of the hydrophobicity of both the gallate derivative and the micelle core on release rate, recording a variety of release patterns. Overall, PCL/F127/PCL and PCL/F68/PCL appear as suitable nanocarriers of potent antioxidant agents in a wide range of polarities, which may be useful for diverse therapeutic applications.
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile , Santiago 7820436, Chile.|Departamento de Ciencias Químicas y Recursos Naturales, Facultad de Ingeniería y Ciencias, Universidad de La Frontera , Temuco 4811230, Chile.
authors.forename: Irma
authors.initials: I
authors.lastname: Fuentes
authors.affiliation: Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.|Michigan State University, Radiology , 610 West Ottawa Street, Apartment 811, Lansing, Michigan 48933, United States.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Blanco-Fernandez
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile , Santiago 7820436, Chile.
authors.forename: Nancy
authors.initials: N
authors.lastname: Alvarado
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile , Santiago 7820436, Chile.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Leiva
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile , Santiago 7820436, Chile.
authors.forename: Deodato
authors.initials: D
authors.lastname: Radić
authors.affiliation: Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.affiliation: Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D041702:BALB 3T3 Cells; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000737:chemistry; D065546:Drug Liberation; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D010316:Particle Size; D010851:Picrates / Q000737:chemistry; D020442:Poloxamer / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility
chemical_list: D000975:Antioxidants; D001672:Biocompatible Materials; D001713:Biphenyl Compounds; D008823:Micelles; D010851:Picrates; D011091:Polyesters; C000620792:poly(epsilon-caprolactone)-b-poloxamer-b-poly(epsilon-caprolactone); D020442:Poloxamer; C048734:ethyl gallate; C052082:methyl gallate; D005707:Gallic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl