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Development of morin/hydroxypropyl-β-cyclodextrin inclusion complex: Enhancement of bioavailability, antihyperalgesic and anti-inflammatory effects

Lima, Bruno dos Santos, Campos, Caio de Alcântara, da Silva Santos, Anna Clara Ramos, Santos, Victória Caroline Nunes, Trindade, Gabriela das Graças Gomes, Shanmugam, Saravanan, Pereira, Erik Willyame Menezes, Marreto, Ricardo Neves, Duarte, Marcelo Cavalcante, Almeida, Jackson Roberto Guedes da Silva, Quintans, Jullyana de Souza Siqueira, Quintans, Lucindo José, Araújo, Adriano Antunes de Souza
Food and chemical toxicology 2019 v.126 pp. 15-24
Fourier transform infrared spectroscopy, anti-inflammatory activity, antioxidants, bioavailability, carrageenan, cell movement, cyclodextrins, differential scanning calorimetry, flavonoids, freeze drying, high performance liquid chromatography, leukocytes, mice, models, nuclear magnetic resonance spectroscopy, pain, pharmacokinetics, pleurisy, rats, scanning electron microscopy, solubility, somatosensory disorders, tumor necrosis factor-alpha
Morin is a flavonoid has been reported with several pharmacological effects such as, antioxidant, anti-inflammatory, anticancer, antidiabetic, etc. However, morin has low solubility in water, which decreases the bioavailability and limits its clinical application. In this way, to improve the pharmaceutical properties, morin was complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and its oral bioavailability and anti-inflammatory effects were evaluated. Initially, a phase solubility study was performed, which showed that HP-β-CD would be the better cyclodextrin for the formation of complexes with morin. The morin/HP-β-CD inclusion complex (1:1) was prepared by freeze-drying method. The sample obtained was characterized by DSC, FTIR, PXRD, SEM and 1H NMR techniques, evidencing the formation of morin/HP-β-CD inclusion complex. In addition, complexation efficiency (98.3%) and loading content (17.63%), determined by HPLC demonstrated that morin was efficiently complexed in HP-β-CD. In vitro dissolution study confirmed that morin/HP-β-CD inclusion complex increased the solubility and dissolution rate of morin. The oral bioavailability of the morin/HP-β-CD complex and free morin were evaluated through a pharmacokinetic study in rat plasma. The oral bioavailability of morin complexed with HP-β-CD was increased by 4.20 times compared with the free morin. Hyperalgesia induced by carrageenan and carrageenan-induced pleurisy were carried out in mice to evaluate the antihyperalgesic and anti-inflammatory activities of free morin and inclusion complex. Morin/HP-β-CD inclusion complex showed antihyperalgesic effect in inflammatory pain model and anti-inflammatory effect decreasing leukocyte migration and TNF-α levels at a lower dose than free morin. Therefore, the morin/HP-β-CD inclusion complex improved the solubility, dissolution rate, oral bioavailability, antihyperalgesic and anti-inflammatory effects of morin. In this way, the morin/HP-β-CD inclusion complex exhibits potential for development of new pharmaceutical product for future clinical applications.