The Formation of Self-Assembled Nanoparticles Loaded with Doxorubicin and d-Limonene for Cancer Therapy.
The Formation of Self-Assembled Nanoparticles Loaded with Doxorubicin and d-Limonene for Cancer Therapy.
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DOI：
10.1021/acsomega.2c04238
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发表时间：
2022-11-22
期刊：
影响因子：
4.1
通讯作者：
Maqboul, Lana
中科院分区：
文献类型：
--
作者：
Assali, Mohyeddin;Jaradat, Nidal;Maqboul, Lana
自组装纳米颗粒具有独特的性质，在开发成功的药物递送系统中具有潜在的应用。多柔比星（DOX）是一种重要的蒽环类抗肿瘤化疗药物。然而，它具有严重的剂量依赖性心脏毒性。d-柠檬烯是许多柑橘油的主要成分，其被认为是抗自由基产生抗氧化活性的特异性单萜。在此，我们的目的是设计三种类型的自组装纳米递送系统（纳米乳液，囊泡，和聚乳酸纳米粒子）装载DOX和d-柠檬烯，以提高溶解的d-柠檬烯，并提供抗氧化活性与优异的抗癌活性。如通过动态光散射和透射电子显微镜所证实的，成功地制备了纳米颗粒，其直径尺寸分别为52、180和257 nm，用于DOX负载的纳米乳液、囊泡和聚乳酸纳米颗粒。在所有情况下，zeta电位值均高于-30 mV，这证实了稳定纳米颗粒的形成。DOX的负载效率在DOX负载的纳米乳液的情况下是最高的（75.8%），其次是囊泡（62.8%），并且最低的是在聚乳酸纳米颗粒的情况下，百分比为50.2%。载DOX纳米粒的体外释放研究显示阿霉素的持续释放曲线，在载DOX的PDLLA纳米粒的情况下释放最高。所有开发的纳米颗粒的动力学释放模型是Peppas-Sahlin模型，证明了DOX通过Fickian扩散现象释放。此外，所有开发的纳米颗粒保持d-柠檬烯的抗氧化活性。载药纳米粒的细胞毒性研究表明，载药纳米乳剂和聚乳酸纳米粒具有浓度依赖性抗癌活性，且具有优异的抗癌活性。这些纳米颗粒将在体内进一步研究，以证明d-柠檬烯与DOX组合的心脏保护作用。
Self-assembled nanoparticles present unique properties that have potential applications in the development of a successful drug delivery system. Doxorubicin (DOX) is an important anti-neoplastic anthracycline chemotherapeutic drug widely described. However, it suffers from serious dose-dependent cardiotoxicity. d-Limonene is a major constituent of numerous citrus oils that is considered a specific monoterpene against free radicals producing antioxidant activity. Herein, we aimed to design three types of self-assembled nanodelivery systems (nanoemulsion, niosomes, and polylactide nanoparticles) for loading both DOX and d-limonene to enhance the solubilization of d-limonene and provide antioxidant activity with excellent anticancer activity. As confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The zeta potential values were above −30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release model for all developed nanoparticles was the Peppas–Sahlin model, demonstrating DOX release through Fickian diffusion phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of d-limonene. The cytotoxicity study of the DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the cardioprotective effect of d-limonene in combination with DOX.
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