2. Academic Validation
  3. A "Ship-in-a-Bottle" strategy to create folic acid nanoclusters inside the nanocages of γ-cyclodextrin metal-organic frameworks

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

  • Int J Pharm. 2019 Feb 10;556:89-96. doi: 10.1016/j.ijpharm.2018.11.074.
Jian Xu 1,  Li Wu 2,  Tao Guo 3,  Guoqing Zhang 4,  Caifen Wang 3,  Haiyan Li 3,  Xue Li 5,  Vikramjeet Singh 6,  Weidong Chen 7,  Ruxandra Gref 8,  Jiwen Zhang 9
Affiliations

Affiliations

  • 1 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai 264005, China.
  • 3 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
  • 4 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; School of Pharmaceutical Sciences, Anhui University of Chinese Medicine, Hefei 230012, China.
  • 5 Institut de Sciences Moléculaires d'Orsay, Université Paris-Saclay, UMR CNRS 8214, 91400 Orsay Cedex, France.
  • 6 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; Institut de Sciences Moléculaires d'Orsay, Université Paris-Saclay, UMR CNRS 8214, 91400 Orsay Cedex, France.
  • 7 School of Pharmaceutical Sciences, Anhui University of Chinese Medicine, Hefei 230012, China. Electronic address: anzhongdong@126.com.
  • 8 Institut de Sciences Moléculaires d'Orsay, Université Paris-Saclay, UMR CNRS 8214, 91400 Orsay Cedex, France. Electronic address: ruxandra.gref@u-psud.fr.
  • 9 Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jwzhang@simm.ac.cn.
PMID: 30528633 DOI: 10.1016/j.ijpharm.2018.11.074
Abstract

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.

Keywords

Drug loading; Folic acid; Nanoclusters; Ship-in-a-Bottle; γ-Cyclodextrin metal-organic frameworks.

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