Synthesis and controlled curcumin supramolecular complex release from pH-sensitive modified gum-arabic-based hydrogels. Issue 115 (3rd November 2015)

• Record Type: Journal Article
• Authors: Gerola, Adriana P.; Silva, Danielle C.; Jesus, Sandra; Carvalho, Rui A.; Rubira, Adley F.; Muniz, Edvani C.; Borges, Olga; Valente, Artur J. M.
• Is Part Of: RSC advances. Volume 5:Issue 115(2015)
• Page Start: 94519
• Page End: 94533
• Publication Date: 2015-11-03
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5ra14331d
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Delivery of a curcumin supramolecular complex from pH-responsive gum arabic-based hydrogels. Abstract : Curcumin (CUR) is a polyphenolic compound including a beta-diketone moiety, which is associated with numerous pharmacological activities, but applications are limited due to its low water solubility. Thus, in this work some inclusion complexes of CUR with alpha-cyclodextrin (α-CD) and beta-cyclodextrin (β-CD) were prepared using different host : guest proportions to improve drug solubilization in biological fluids. The formation of these complexes was confirmed by 1 H NMR and thermogravimetric analysis. The stoichiometries of the CUR/α-CD and CUR/β-CD complexes were 1 : 1 and 1 : 2 and the association constants were 344 mol −1 L and 7.2 × 10 7 mol −2 L 2 for α-CD and β-CD, respectively. The major stability of the CUR/β-CD complex is justified by an inclusion of the aromatic ring inside the CD cavity, whilst in the case of α-CD-complexes the interactions occur via H-bridges, showing the latter complexes' slow exchange on the NMR time-scale. Even so, the solubility of curcumin complexes is clearly controlled by the solubility of CDs, showing the highest solubility for CUR/α-CD complexes. Hydrogels of modified gum arabic containing CUR/α-CD (1 : 4) were obtained and used for controlled release of CUR in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). The kinetics of release was pH-responsive and the percentage of CUR released was ca. 97% in SIF and 6.7% in SGF. For the toxicity studies on undifferentiated Caco-2 cells, IC50 s of 63.4 ± 14.4 μg mL −1 and 85.2 ± 14.9 μg mL −1 for CUR and CUR/α-CD (1 : 4), respectively, were obtained. The toxicity of these samples on differentiated Caco-2 cells was lower than on undifferentiated cells. Additionally, the CUR incorporated into hydrogels showed no toxic effects on differentiated and undifferentiated Caco-2 cells, indicating the pharmaceutical potential of three-dimensional matrices of GAm for controlled release of CUR complexed with cyclodextrin.