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Purpose <p>This study aimed to construct three UiO‑66‑supported Nilotinib (NIL) polymorph systems (Form A, Form X, and amorphous) and address whether UiO‑66 can effectively stabilize NIL polymorphs, enhance their dissolution performance while preserving the intrinsic polymorph‑dependent dissolution behaviors, and elucidate the solubilization mechanisms involved.</p> Methods <p>The UiO‑66‑supported NIL polymorph systems were prepared by supporting NIL Form A, NIL Form X, and NIL Amorphous on UiO‑66 via mechanical ball milling. The resulting composites were comprehensively characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), nitrogen adsorption–desorption analysis, and thermogravimetric analysis (TGA). Solubility and dissolution studies were conducted, and accelerated stability testing was performed at 40 °C/75% RH for 180 days.</p> Results <p>DSC confirmed that the NIL polymorphs were stabilized as nanoscale crystalline domains within the UiO‑66‑supported systems. SEM revealed that UiO‑66 nanoparticles primarily coated the surfaces of the NIL polymorphs, while nitrogen adsorption–desorption analysis showed distinct pore‑blocking behaviors. TGA demonstrated that the thermal stability of the NIL polymorphs was enhanced upon incorporation into UiO‑66. The UiO‑66‑supported systems markedly improved the dissolution performance of the NIL polymorphs while retaining their intrinsic dissolution profiles. Among the systems, UiO‑66‑supported NIL Form X exhibited the most favorable dissolution performance, providing a 44.08‑fold increase in solubility compared with NIL Form A and the highest C<sub>max</sub> and equilibrium concentration at pH 6.5. Accelerated stability testing further showed that the UiO‑66‑supported NIL amorphous system maintained excellent physical and chemical stability over 180 days.</p> <p>UiO‑66 serves as an effective carrier for delivering NIL polymorphs, enabling polymorph stabilization, significant dissolution enhancement, and preservation of polymorph‑specific dissolution behavior. These findings lay a foundation for the development of polymorph‑based MOF drug delivery systems and broaden the formulation possibilities for polymorphic drugs.</p> Graphical Abstract <p></p>

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Mechanochemical Fabrication of UiO-66-Supported Nilotinib Polymorphs for Drug Delivery

  • 期刊论文

  • 发表日期：

    2026年4月28日

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  • Junjie Peng,
  • Youqin Wang,
  • Jianghao Yuan,
  • Mingkang Xu,
  • Da Wu,
  • Bokai Kong,
  • Zhijie Zhang,
  • Xiangjun Shi,
  • Weike Su

摘要

Purpose

This study aimed to construct three UiO‑66‑supported Nilotinib (NIL) polymorph systems (Form A, Form X, and amorphous) and address whether UiO‑66 can effectively stabilize NIL polymorphs, enhance their dissolution performance while preserving the intrinsic polymorph‑dependent dissolution behaviors, and elucidate the solubilization mechanisms involved.

Methods

The UiO‑66‑supported NIL polymorph systems were prepared by supporting NIL Form A, NIL Form X, and NIL Amorphous on UiO‑66 via mechanical ball milling. The resulting composites were comprehensively characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), nitrogen adsorption–desorption analysis, and thermogravimetric analysis (TGA). Solubility and dissolution studies were conducted, and accelerated stability testing was performed at 40 °C/75% RH for 180 days.

Results

DSC confirmed that the NIL polymorphs were stabilized as nanoscale crystalline domains within the UiO‑66‑supported systems. SEM revealed that UiO‑66 nanoparticles primarily coated the surfaces of the NIL polymorphs, while nitrogen adsorption–desorption analysis showed distinct pore‑blocking behaviors. TGA demonstrated that the thermal stability of the NIL polymorphs was enhanced upon incorporation into UiO‑66. The UiO‑66‑supported systems markedly improved the dissolution performance of the NIL polymorphs while retaining their intrinsic dissolution profiles. Among the systems, UiO‑66‑supported NIL Form X exhibited the most favorable dissolution performance, providing a 44.08‑fold increase in solubility compared with NIL Form A and the highest Cmax and equilibrium concentration at pH 6.5. Accelerated stability testing further showed that the UiO‑66‑supported NIL amorphous system maintained excellent physical and chemical stability over 180 days.

UiO‑66 serves as an effective carrier for delivering NIL polymorphs, enabling polymorph stabilization, significant dissolution enhancement, and preservation of polymorph‑specific dissolution behavior. These findings lay a foundation for the development of polymorph‑based MOF drug delivery systems and broaden the formulation possibilities for polymorphic drugs.

Graphical Abstract