Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Abstract

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from STV@CD-MOF (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF (1:1) owing to nanoclusters formation. The bioavailability of STV@CD-MOF (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of STV@CD and STV@CD-MOF (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.

The Systems of Naringenin with Solubilizers Expand Its Capability to Prevent Neurodegenerative Diseases

“…These considerations are supported by the results of studies on other substances in the literature. Chen et al used a cyclodextrin metal-organic framework to improve the solubility of isosteviol and to enhance the bioavailability in male Sprague-Dawley rats by 8.67-fold [ 44 ]. Wu et al increased the solubility of biochanin A, according to the micelles preparation with Pluronic F127 and Plasdone S630 [ 45 ].…”

Synthesis and potential applications of cyclodextrin-based metal–organic frameworks: a review

“…Cyclodextrins consist of six, seven, or eight D-glucopyranose units linked together by α-1,4 glycosidic bonds in the form of hollow cylindrical stereocyclic structures, called α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, respectively, with a hydrophilic outer surface and hydrophobic inner cavity (Fig. 3 ) (Agafonov et al 2022 ; Chen et al 2021a ; Chen et al 2021b ; Petitjean et al 2021 ). The hydrophobic inner cavity diameters of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin range from 4.7 to 5.3, 6.0 to 6.5, and 7.5 to 8.3 Å, respectively (Wankar et al 2020 ).…”

“…In the cyclodextrin-based metal–organic framework, two distinct isosteviol-cyclodextrin-based metal–organic framework loading molar ratios of 0.5:1 and 1:1 were assessed. Furthermore, the oral bioavailability of the isosteviol-cyclodextrin-based metal–organic framework (1:1) was compared to that of the isosteviol-cyclodextrin-based metal–organic framework (0.5:1) and pure isosteviol (Chen et al 2021b ). The isosteviol solubility was less than 20.00 ng/mL at pH 1.0 and 4.5 but rose to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a considerable pH dependence.…”

“…The isosteviol solubility was less than 20.00 ng/mL at pH 1.0 and 4.5 but rose to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a considerable pH dependence. Additionally, the bioavailability of isosteviol-cyclodextrin-based metal–organic framework (1:1) in rats was 8.67-fold greater than isosteviol and 1.32- and 1.27-fold larger than isosteviol-cyclodextrin and isosteviol-cyclodextrin-based metal–organic framework (0.5:1), respectively (Chen et al 2021b ). Systematically, when isosteviol in the cyclodextrin-based metal–organic framework was found at a low loading ratio, the inclusion process was dominant, whilst the nanocluster mechanism was responsible for improving bioavailability at a high loading ratio (Chen et al 2021b ).…”

Stimuli-responsive cyclodextrin-based supramolecular assemblies as drug carriers

“…[14][15][16][17][18] The interior cavity, which is the slightly nonpolar cavity of CDs in an aqueous environment, is more prone to encapsulating guest molecules with less polarity, and this makes CDs an ideal platform to deliver hydrophobic drugs. [19][20][21][22] Unique structures prepared by CDs, such as rotaxanes and polyrotaxanes, have been widely applied in biomedical applications as well. 23,24 Furthermore, with the encapsulation of guest molecules such as azobenzene (Azo) and ferrocene (Fc), CDs can be constructed into functional materials for precise targeted delivery of drugs or other diagnosis agents.…”