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

被引：67

作者：

Lima, Bruno dos Santos ^{[1
]}

Campos, Caio de Alcantara ^{[1
]}

Ramos da Silva Santos, Anna Clara ^{[1
]}

Nunes Santos, Victoria Caroline ^{[1
]}

Gomes Trindade, Gabriela das Gracas ^{[1
]}

Shanmugam, Saravanan ^{[1
]}

Menezes Pereira, Erik Willyame ^{[2
]}

Marreto, Ricardo Neves ^{[3
]}

Duarte, Marcelo Cavalcante ^{[1
]}

Guedes da Silva Almeida, Jackson Roberto ^{[4
]}

Siqueira Quintans, Jullyana de Souza ^{[2
]}

Quintans, Lucindo Jose, Jr. ^{[2
]}

de Souza Araujo, Adriano Antunes ^{[1
]}

机构：

[1] Univ Fed Sergipe, Dept Pharm, BR-49100000 Sao Cristovao, SE, Brazil

[2] Univ Fed Sergipe, Dept Physiol, Sao Cristovao, SE, Brazil

[3] Univ Fed Goias, Fac Pharm, Goiania, Go, Brazil

[4] Fed Univ San Francisco Valley, Ctr Studies & Res Med Plants, Petrolina, PE, Brazil

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2019年 / 126卷

关键词：

Morin; Hydroxypropyl-beta-cyclodextrin; Bioavailability; Antihyperalgesic; Anti-inflammatory; PHYSICOCHEMICAL CHARACTERIZATION; MORIN; DISSOLUTION; SOLUBILITY; NANOPARTICLES; APIGENIN; SYSTEM; MODEL; CD;

D O I：

10.1016/j.fct.2019.01.038

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

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-beta-cyclodextrin (HP-beta-CD) and its oral bioavailability and anti-inflammatory effects were evaluated. Initially, a phase solubility study was performed, which showed that HP-beta-CD would be the better cyclodextrin for the formation of complexes with morin. The morin/HP-beta-CD inclusion complex (1:1) was prepared by freeze-drying method. The sample obtained was characterized by DSC, FTIR, PXRD, SEM and H-1 NMR techniques, evidencing the formation of morin/HP-beta-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-beta-CD. In vitro dissolution study confirmed that morin/HP-beta-CD inclusion complex increased the solubility and dissolution rate of morin. The oral bioavailability of the morin/HP-beta-CD complex and free morin were evaluated through a pharmacokinetic study in rat plasma. The oral bioavailability of morin complexed with HP-beta-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-beta-CD inclusion complex showed antihyperalgesic effect in inflammatory pain model and anti-inflammatory effect decreasing leukocyte migration and TNF-alpha levels at a lower dose than free morin. Therefore, the morin/HP-beta-CD inclusion complex improved the solubility, dissolution rate, oral bioavailability, antihyperalgesic and anti-inflammatory effects of morin. In this way, the morin/HP-beta-CD inclusion complex exhibits potential for development of new pharmaceutical product for future clinical applications.

引用

页码：15 / 24

页数：10

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