Exploring the enhanced stability and therapeutic efficacy of Sorafenib-Cyclodextrin inclusion complex

Abstract

Sorafenib (Soraf) is a second-generation tyrosine kinase inhibitor repurposed against different cancers by working on various molecular pathways, playing a vital role in cancer cell proliferation. Sorafenib is a BCS class II drug, and its low solubility further hinders its bioavailability and results in reduced therapeutic efficacy. Therefore, in this study, we aim to explore the potential of β-cyclodextrins (β-CD) derivatives to form an inclusion complex with sorafenib to enhance sorafenib's solubility, stability, and therapeutic efficacy. Our findings suggest that HP-β-CD portrayed a higher affinity towards sorafenib than SBE-β-CD and significantly improved the solubility of sorafenib. Additionally, spectroscopic analysis and solid-state studies provided valuable information regarding the intermolecular interaction between sorafenib and HP-β-CD.Furthermore, the stability of sorafenib in biological fluids and under physiological conditions was maintained under the influence of the inclusion complex, whereas plain sorafenib degraded quickly. In addition, β-CD complexation significantly improved sorafenib's intestinal permeability, as shown in physiologically relevant EpiIntestinal® models. Lastly, the sorafenib inclusion complex demonstrated increased cytotoxicity in NSCLC and HCC cell lines. This study shows the potential of HP-β-CD to improve the solubility and therapeutic efficacy of sorafenib, thus extending its clinical application.