Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, 6th of October City, Giza, Egypt.
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Life Sci. 2022 Sep 15;305:120731. doi: 10.1016/j.lfs.2022.120731. Epub 2022 Jun 24.
Breast cancer (BC) is considered the leading cause of mortality and morbidity among adult women worldwide, and it is associated with many genetic or hormonal factors. Despite the advanced therapeutic and theranostic strategies for BC treatment, cancer metastasis and relapse are often observed among patients which lead to therapeutic failure. Accordingly, among the repositioned medication against BC proliferation is neurokinin receptor antagonists and iron chelating agents especially rolapitant HCl (RP) and deferasirox (DFO), respectively. However, RP and DFO are classified as class II with low aqueous solubility. Both drugs were nanoformulated into PEGylated lipid nanocapsules (LNCs) for enhancing their aqueous solubility and augmenting their efficacy. RP-LNCs, DFO-LNCs and their combinations were evaluated according to particle size (PS), zeta potential, polydispersity index (PDI) and surface morphology. Importantly, the antitumor effect of these novel molecules and their nanoforms was evaluated against the suppression of Ehrlich Ascites tumor model using female mice. Results revealed that RP-LNCs, DFO-LNCs and RP/DFO-LNCs exerted PS from 45.23 ± 3.54 to 60.1 ± 3.32 nm with PDI around 0.20 which indicates homogenous particles distribution. Also, RP-LNCs, DFO-LNCs and RP/DFO-LNCs displayed surface charges of +16.6 ± 6.9, -13.3 ± 5.82 and - 20.2 ± 5.40 mV, respectively. The obtained LNCs conferred a high potent cytotoxic effect against MCF7 cancer cells as compared to parent drugs, with IC of 10.86 ± 0.89, 3.34 ± 0.99 and 2.24 ± 0.97 μg/mL for RP-LNCs, DFO-LNCs and RP/DFO-LNCs, respectively. The in-vivo pharmacodynamics effect of the developed nano-formulations showed superior antitumor effect for the individual drugs rather than their combinations as compared to the control group. The current study confirmed the potential of RP and DFO nanoforms as promising therapeutic agents for BC treatment.
乳腺癌（BC）被认为是全球成年女性死亡和发病的主要原因，与许多遗传或激素因素有关。尽管针对 BC 治疗的治疗和治疗策略已经很先进，但癌症转移和复发在患者中经常观察到，这导致治疗失败。因此，在针对 BC 增殖的重新定位药物中，神经激肽受体拮抗剂和铁螯合剂（尤其是盐酸罗哌丁（RP）和地拉罗司（DFO））是特别有效的。然而，RP 和 DFO 被归类为 II 类，水溶性低。这两种药物均被纳米化为聚乙二醇化脂质纳米胶囊（LNC），以提高其水溶性并增强其功效。根据粒径（PS）、zeta 电位、多分散指数（PDI）和表面形态，对 RP-LNC、DFO-LNC 及其组合进行了评估。重要的是，使用雌性小鼠评估了这些新型分子及其纳米形式对抑制艾氏腹水肿瘤模型的抗肿瘤作用。结果表明，RP-LNC、DFO-LNC 和 RP/DFO-LNC 的 PS 从 45.23±3.54 增加到 60.1±3.32nm，PDI 约为 0.20，表明颗粒分布均匀。此外，RP-LNC、DFO-LNC 和 RP/DFO-LNC 的表面电荷分别为+16.6±6.9、-13.3±5.82 和-20.2±5.40mV。与母体药物相比，所得 LNC 对 MCF7 癌细胞具有很高的细胞毒性作用，IC 分别为 10.86±0.89μg/mL、3.34±0.99μg/mL 和 2.24±0.97μg/mL，对于 RP-LNC、DFO-LNC 和 RP/DFO-LNC。所开发的纳米制剂的体内药效学作用表明，与对照组相比，单个药物的抗肿瘤作用优于其组合。本研究证实了 RP 和 DFO 纳米制剂作为治疗 BC 的有前途的治疗剂的潜力。
