A “Ship-in-a-Bottle” strategy to create folic acid nanoclusters inside the nanocages of γ-cyclodextrin metal-organic frameworks

Publication date: Available online 8 December 2018Source: International Journal of PharmaceuticsAuthor(s): Jian Xu, Li Wu, Tao Guo, Guoqing Zhang, Caifen Wang, Haiyan Li, Xue Li, Vikramjeet Singh, Weidong Chen, Ruxandra Gref, Jiwen ZhangAbstractAssembled between γ-cyclodextrins (CD) and potassium ions, γ-cyclodextrin metal-organic frameworks (CD-MOF) create spatially extended and ordered cage-like structures. Herein, it was demonstrated that folic acid (FA), a model molecule, could be densely packed inside CD-MOF reaching 2:1 FA:CD molar ratio. This “Ship-in-Bottle” strategy leads to a 1450 fold increase of the apparent solubility of FA. Moreover, the bioavailability of FA inside CD-MOF in rats was enhanced by a factor of 1.48 as compared to free FA. The unique mechanism of FA incorporation in the CD-MOF 3D network was also explored, which was different from the conventional CD inclusion complexation. Taylor dispersion investigations indicated that FA was incorporated on the basis of a two-component model, which was further supported by a set of complementary methods, including SEM, XRPD, BET, SR-FTIR, SAXS and molecular simulation. The hypothesized mechanism suggested that: i) tiny FA nanoclusters formed inside the hydrophilic cavities and onto the surface of CD-MOF and ii) FA was included inside dual-CD units in CD-MOF. In a nutshell this dual incorporation mechanism is an original approach to dramatically increase the drug apparent solubility and bioavailability, and...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research