Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.
In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections.
Laboratorio de Reología, Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, Blv. M. García Barragán 1421 Guadalajara, Jalisco, Mexico.
Edgar B
EB
Figueroa-Ochoa
Grupo de Física de Coloides y Polímeros, Departamento de Física de la Materia Condensada; Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Eva M
EM
Villar-Alvarez
Grupo de Física de Coloides y Polímeros, Departamento de Física de la Materia Condensada; Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Adriana
A
Cambón
School of Chemistry, University of Manchester, Manchester M13 9PL, United Kingdom.
Dharmista
D
Mistry
Servicio de Microbiología y Parasitología, Complejo Hospitalario de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
José
J
Llovo
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL, United Kingdom.
David
D
Attwood
Grupo de Física de Coloides y Polímeros, Departamento de Física de la Materia Condensada; Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: silvia.barbosa@usc.es.
Silvia
S
Barbosa
Laboratorio de Reología, Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, Blv. M. García Barragán 1421 Guadalajara, Jalisco, Mexico.
J F Armando
JF
Soltero
Grupo de Física de Coloides y Polímeros, Departamento de Física de la Materia Condensada; Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: pablo.taboada@usc.es.
Pablo
P
Taboada
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations; D005782:Gels; D008823:Micelles; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology*; D011090:Polyenes / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*
D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D005782:Gels; D008823:Micelles; D010087:Oxides; D011090:Polyenes; D011108:Polymers; D011092:Polyethylene Glycols; C008952:polybutene
Antifungal activity; Controlled release; Gelling network; Polymeric micelle; Reverse block copolymers