Dovitinib (DOV) is a tyrosine kinase inhibitor affecting the vascular endothelial growth factor and antiangiogenic activity. It has been studied in tumor and carcinoma treatment. However, its therapeutic usefulness is hampered by its very low aqueous solubility. In this present study, cyclodextrins (CDs) and polymers were used to solubilize DOV. The DOV/CD complexes were characterized by 1 H-NMR, and formation of nano- and microparticles by dynamic light scattering and in vitro permeation studies. In aqueous CD media DOV was stable during autoclaving at low γCD concentrations. In aqueous γCD solutions DOV displayed B s -type phase solubility profile. Water-soluble polymers enhanced DOV solubility in aqueous CD solutions through ternary complex formations and formation of complex aggregates. CD derivatives were also able to increase the DOV solubility but the concentration of complex nanoparticles was relatively low. In comparison to the binary DOV/γCD complexes, the permeation flux of ternary DOV/γCD/polymer complexes increased while their apparent permeability coefficient values decreased.

中文翻译：

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多维替尼/环糊精复合物及其聚集体的溶解和体外渗透

多维替尼 (DOV) 是一种酪氨酸激酶抑制剂，可影响血管内皮生长因子和抗血管生成活性。它已在肿瘤和癌症治疗中进行了研究。然而，其极低的水溶性阻碍了其治疗用途。在本研究中，环糊精 (CD) 和聚合物用于溶解 DOV。DOV/CD 复合物通过 1 H-NMR 表征，并通过动态光散射和体外渗透研究形成纳米和微粒。在水相 CD 介质中，DOV 在低 γCD 浓度下高压灭菌期间是稳定的。在 γCD 水溶液中，DOV 显示出 B s 型相溶解度曲线。水溶性聚合物通过三元复合物的形成和复杂聚集体的形成，增强了 DOV 在 CD 水溶液中的溶解度。CD 衍生物也能够增加 DOV 溶解度，但复杂纳米粒子的浓度相对较低。与二元DOV/γCD复合物相比，三元DOV/γCD/聚合物复合物的渗透通量增加，而表观渗透系数值下降。