Nanoformulation Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Nanoformulation Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India; Formulation Research Lab., Advance Nanomeds, Plot No. 142/20A, NSEZ, Noida 201305, UP, India.
Colloids Surf B Biointerfaces. 2020 Mar;187:110628. doi: 10.1016/j.colsurfb.2019.110628. Epub 2019 Nov 12.
Doxorubicin (DOX) is commonly used for the treatment of many types of cancers but its cardiotoxicity, owing to free radical formation, limits its clinical use. Hesperidin (HES), a flavanone glycoside, has been shown to exert multiple pharmacological actions including cardioprotective effects. Herein, we aim to formulate HES loaded solid lipid nanoparticles (SLNs) using supercritical antisolvent (SAS) technology to improve the oral delivery of HES. Process parameters were optimized to produce small size (175.3 ± 3.6 nm) HES-SLNs with high encapsulation efficiency (87.6 ± 3.8 %). DSC and XRD showed that HES is amorphously dispersed in SLNs. Compared to HES, HES-SLNs resulted in a nearly 20-fold increase in aqueous solubility and a nearly 5-fold increase in apparent permeability. Pharmacokinetics in rats revealed nearly 4.5-fold higher bioavailability of HES from SLN formulation compared to HES suspension. Data showed that HES-SLN significantly attenuated DOX-induced cardiotoxicity through lowering creatine kinase-muscle/brain, cardiac troponin I and improving histopathological scores as compared to the DOX group. HES-SLN also decreased malondialdehyde, increased catalase and superoxide dismutase of rats' heart to levels relatively comparable to control. Marked reductions in caspase-3 were also observed following HES-SLN treatment. Conclusively, these results describe a cardioprotective effect for HES-SLN against DOX-induced cardiotoxicity likely facilitated via suppression of oxidative stress and apoptosis.
多柔比星（DOX）常用于治疗多种类型的癌症，但由于自由基的形成，其心脏毒性限制了其临床应用。橙皮苷（HES），一种类黄酮糖苷，已被证明具有多种药理作用，包括心脏保护作用。在此，我们旨在使用超临界抗溶剂（SAS）技术制备 HES 负载的固体脂质纳米粒（SLNs），以改善 HES 的口服递送。优化工艺参数以生产小尺寸（175.3 ± 3.6nm）、高包封效率（87.6 ± 3.8%）的 HES-SLNs。DSC 和 XRD 表明 HES 无定形分散在 SLNs 中。与 HES 相比，HES-SLNs 使 HES 的水溶解度增加近 20 倍，表观渗透率增加近 5 倍。大鼠药代动力学研究表明，与 HES 混悬剂相比，HES-SLN 使 HES 的生物利用度提高近 4.5 倍。数据表明，与 DOX 组相比，HES-SLN 通过降低肌酸激酶-肌肉/脑、心肌肌钙蛋白 I，并改善组织病理学评分，显著减轻 DOX 诱导的心脏毒性。HES-SLN 还降低了大鼠心脏中的丙二醛，增加了过氧化氢酶和超氧化物歧化酶，使其水平相对接近对照。在 HES-SLN 治疗后，还观察到 caspase-3 的明显减少。总之，这些结果描述了 HES-SLN 对 DOX 诱导的心脏毒性的心脏保护作用，这可能是通过抑制氧化应激和细胞凋亡来实现的。
