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

Autor: Weidong Chen, Xue Li, Haiyan Li, Vikramjeet Singh, Ruxandra Gref, Tao Guo, Jian Xu, Jiwen Zhang, Li Wu, Caifen Wang, Guoqing Zhang
Přispěvatelé: Hangzhou Dianzi University (HDU), Department of Veterinary Bioscience, Ohio State University [Columbus] (OSU)-Center for Retrovirus Research, Institute of Computing Technology, Chinese Academy of Sciences,College of Hunan, Institute of Analytical Science, Institut des Sciences Moléculaires d'Orsay (ISMO), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Physico-Chimie de l'Atmosphère (LPCA), Université du Littoral Côte d'Opale (ULCO)-Centre National de la Recherche Scientifique (CNRS), Shanghai Institute of Materia Medica, Chinese Academy of Sciences [Changchun Branch] (CAS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2019, 556, pp.89-96. ⟨10.1016/j.ijpharm.2018.11.074⟩
ISSN: 0378-5173
Popis: 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.
Databáze: OpenAIRE
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