Enhancing the solubility and bioavailability of Bazedoxifene with varying γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) as delivery vehicles

Abstract

To address the poor solubility and low bioavailability of BCS Class II drugs, exemplified by Bazedoxifene (BZA), in aqueous environments, we utilized γ-cyclodextrin (γ-CD), γ-cyclodextrin metal-organic frameworks (3D-CD-MOFs), and γ-cyclodextrin metal-organic framework nanosheets (2D-CD-MOFs) as carriers for BZA, and investigated their effects on the drug's solubility and bioavailability. The synthesis and drug-loading processes were optimized, and the impact on the morphology and properties of the CD-MOFs was explored. Molecular docking simulations were conducted to examine the distribution and binding sites of BZA within the CD-MOFs. Finally, the drug loading capacity, solubility, in vitro release, and pharmacokinetics were assessed. The experimental results indicated that the 2D-CD-MOF possessed a high BZA loading capacity and significantly improved drug solubility and bioavailability. The bioavailability of BZA@2D-CD-MOF was 4.47, 1.38 and 4.41 times higher than that of BZA, BZA@3D-CD-MOF and BZA@γ-CD groups, respectively. This study demonstrates that 2D-CD-MOF nanosheets significantly outperform 3D-CD-MOFs and γ-CD in enhancing BZA solubility and bioavailability, exhibiting favorable safety profiles. Employing γ-cyclodextrin metal-organic framework nanosheets for BZA loading presents considerable feasibility and potential for enhancing its solubility and bioavailability.