A “Ship-in-a-Bottle” strategy to create folic acid nanoclusters inside the nanocages of γ-cyclodextrin metal-organic frameworks - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue International Journal of Pharmaceutics Année : 2019

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

Jian Xu
Li Wu
  • Fonction : Auteur
  • PersonId : 762743
  • IdRef : 190923008
Tao Guo
  • Fonction : Auteur
Caifen Wang
  • Fonction : Auteur
Xue Li
Ruxandra Gref
Jiwen Zhang

Résumé

Assembled 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-a-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 could be a promising strategy for other poorly soluble drugs.
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Dates et versions

hal-02367425 , version 1 (17-11-2019)

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Jian Xu, Li Wu, Tao Guo, Guoqing Zhang, Caifen Wang, et al.. A “Ship-in-a-Bottle” strategy to create folic acid nanoclusters inside the nanocages of γ-cyclodextrin metal-organic frameworks. International Journal of Pharmaceutics, 2019, 556, pp.89-96. ⟨10.1016/j.ijpharm.2018.11.074⟩. ⟨hal-02367425⟩
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