Enhanced antitumor efficacy of lapachol-loaded nanoemulsion in breast cancer tumor model.
Enhanced antitumor efficacy of lapachol-loaded nanoemulsion in breast cancer tumor model.
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DOI：
10.1016/j.biopha.2020.110936
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
de Barros ALB
中科院分区：
文献类型：
--
作者：
Mendes Miranda SE;Alcântara Lemos J;Fernandes RS;Silva JO;Ottoni FM;Townsend DM;Rubello D;Alves RJ;Cassali GD;Ferreira LAM;de Barros ALB
拉帕胆碱 (LAP) 是一种天然化合物，具有多种生物特性，包括抗癌活性。然而，由于其水溶性低和潜在的不良副作用，其临床应用受到限制。纳米乳剂是药物输送系统，可以帮助疏水性药物的给药，提高其生物利用度并防止降解。因此，本研究旨在制备负载LAP的纳米乳（NE-LAP），并评估其抗肿瘤活性。为此，使用热均质方法制备纳米乳液，并通过低温透射电子显微镜（cryo-TEM）进行形态表征。通过DLS评估平均直径、多分散指数和zeta电位，通过HPLC测量包封率。此外，还测定了短期储存稳定性、体外药物释放和溶血情况。此外，还在乳腺癌(4T1)肿瘤模型中评估了99mTc-NE-LAP的药代动力学、毒理学和毒性特性。冷冻透射电镜显示出球形小球，NE-LAP 的物理化学表征显示出均匀稳定的纳米乳液，平均直径约为 170 nm，zeta 电位约为 -20 mV，封装率大于 85%。体外研究证实封装不会损害 LAP 的细胞毒性活性。纳米乳剂成功地被放射性标记，99mTc-NE-LAP 显示出延长的血液循环，并且通过肿瘤与肌肉的比率证实了肿瘤亲和力。此外，NE-LAP 显示出比游离药物更高的抗肿瘤活性，并且治疗没有导致任何毒性迹象。因此，这些发现表明 NE-LAP 可以被认为是癌症治疗的有效策略。
Lapachol (LAP) is a natural compound with various biological properties, including anticancer activity. However, its clinical application is limited due to the low aqueous solubility and potential adverse side effects. Nanoemulsions are drug delivery systems that can assist in the administration of hydrophobic drugs, increasing their bioavailability and protecting from degradation. Thus, this study aimed to prepare a LAP-loaded nanoemulsion (NE-LAP), and evaluate its antitumor activity. For this purpose, the nanoemulsion was prepared using a hot homogenization method and characterized morphologically by cryogenic transmission electron microscopy (cryo-TEM). Mean diameter, polydispersity index, and zeta potential was evaluated by DLS, encapsulation efficiency was measured by HPLC. Moreover, the short-term storage stability, the drug release and hemolysis in vitro was determined. Additionally, pharmacokinetic, toxicology and toxicity properties of99mTc-NE-LAP were evaluated in a breast cancer (4T1) tumor model. The cryo-TEM showed spherical globules, and the physicochemical characterization of NE-LAP showed a homogeneous stable nanoemulsion with a mean diameter of ~170 nm, zeta potential of around −20 mV, and encapsulation greater than 85 %. In vitro studies validated that encapsulation did not impair the cytotoxicity activity of LAP. The nanoemulsion was successfully radiolabeled and 99mTc-NE-LAP showed prolonged blood circulation and tumor affinity was confirmed by tumor-to-muscle ratio. Moreover, NE-LAP showed higher antitumor activity than the free drug and the treatment did not result in any signs of toxicity. Therefore, these findings suggest that NE-LAP can be considered an effective strategy for cancer treatment.
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影响因子：
7.7
作者：
Epifano, Francesco;Genovese, Salvatore;Kiss, Robert
通讯作者：
Kiss, Robert
DOI：
10.1007/s10555-015-9586-9
发表时间：
2015-12
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
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通讯作者：
Kripke ML
影响因子：
4.9
作者：
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通讯作者：
Hartinger, Christian G.
影响因子：
5.8
作者：
Chen, Lina;Chen, Bingchen;Chen, Jianming
通讯作者：
Chen, Jianming
影响因子：
5.8
作者：
Aherne, GW;Hardcastle, A;Jackman, AL
通讯作者：
Jackman, AL