Budesonide-hydroxypropyl-beta-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels

Author(s)

Santos Akkari, Alessandra Cristina ^[1] ; Ramos Campos, Estefania Vangelie ^[2] ; Keppler, Artur Franz ^[1] ; Fraceto, Leonardo Fernandes ^[2] ; de Paula, Eneida ^[3] ; Tofoli, Giovana Radomille ^[4] ; de Araujo, Daniele Ribeiro ^[1]

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] State Univ Julio de Mesquita Filho, Dept Enviroment Engn, Sorocaba, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Dept Biochem, Campinas, SP - Brazil

^[4] Fac Dent Sao Leopoldo Mand, Campinas, SP - Brazil

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 138, p. 138-147, FEB 1 2016.
• Web of Science Citations: 12

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-beta-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-beta-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-beta-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-beta-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (T-m) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-beta-CD or BUD:HP-beta-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-beta-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-beta-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/26200-9 - Nanostructured hybrid systems for modified release of antiinflammatpry drugs: development and pharmacological evaluation
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants