title: Budesonide-hydroxypropyl-β-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels.
abstract: Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-β-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-β-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc=8662.8 M(-1)), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-β-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-β-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (Tm) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-β-CD or BUD:HP-β-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-β-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-β-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis.
authors.affiliation: Human and Natural Sciences Center, Federal University of ABC, Santo André, SP, Brazil.
authors.forename: Alessandra Cristina
authors.initials: AC
authors.lastname: Santos Akkari
authors.affiliation: Department of Enviroment Engineering, State University "Júlio de Mesquita Filho", Sorocaba, SP, Brazil.
authors.forename: Estefânia Vangelie
authors.initials: EV
authors.lastname: Ramos Campos
authors.affiliation: Human and Natural Sciences Center, Federal University of ABC, Santo André, SP, Brazil.
authors.forename: Artur Franz
authors.initials: AF
authors.lastname: Keppler
authors.affiliation: Department of Enviroment Engineering, State University "Júlio de Mesquita Filho", Sorocaba, SP, Brazil.
authors.forename: Leonardo Fernandes
authors.initials: LF
authors.lastname: Fraceto
authors.affiliation: Department of Biochemistry, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
authors.affiliation: Faculty of Dentistry São Leopoldo Mandic, Campinas, SP, Brazil.
authors.forename: Giovana Radomille
authors.initials: GR
authors.lastname: Tófoli
authors.affiliation: Human and Natural Sciences Center, Federal University of ABC, Santo André, SP, Brazil. Electronic address: daniele.araujo@ufabc.edu.br.
authors.forename: Daniele Ribeiro
authors.initials: DR
authors.lastname: de Araujo
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019819:Budesonide / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism; D065546:Drug Liberation; D006801:Humans; D057446:Hydrodynamics; D020100:Hydrogels / Q000737:chemistry*; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D044367:Phase Transition; D020442:Poloxamer / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D020100:Hydrogels; D008823:Micelles; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D019819:Budesonide
keywords: Budesonide; Cyclodextrin; Hydrogel; Micelle; Poloxamer; Polyrotaxane; Ulcerative colitis