Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas-UNICAMP, Campinas 13083-862, Brazil.
Institute of Biotechnology, Federal University of Uberlandia-UFU, Uberlandia 38405-319, Brazil.
Molecules. 2022 Dec 13;27(24):8838. doi: 10.3390/molecules27248838.
Breast cancer is the neoplasia of highest incidence in women worldwide. Docetaxel (DTX), a taxoid used to treat breast cancer, is a BCS-class-IV compound (low oral bioavailability, solubility and intestinal permeability). Nanotechnological strategies can improve chemotherapy effectiveness by promoting sustained release and reducing systemic toxicity. Nanostructured lipid carriers (NLC) encapsulate hydrophobic drugs in their blend-of-lipids matrix, and imperfections prevent drug expulsion during storage. This work describes the preparation, by design of experiments (2 factorial design) of a novel NLC formulation containing copaiba oil (CO) as a functional excipient. The optimized formulation (NLC) showed approximately 100% DTX encapsulation efficiency and was characterized by different techniques (DLS, NTA, TEM/FE-SEM, DSC and XRD) and was stable for 12 months of storage, at 25 °C. Incorporation into the NLC prolonged drug release for 54 h, compared to commercial DTX (10 h). In vitro cytotoxicity tests revealed the antiproliferative effect of CO and NLC, by reducing the cell viability of breast cancer (4T1/MCF-7) and healthy (NIH-3T3) cells more than commercial DTX. NLC thus emerges as a promising drug delivery system of remarkable anticancer effect, (strengthened by CO) and sustained release that, in clinics, may decrease systemic toxicity at lower DTX doses.
乳腺癌是全球女性发病率最高的肿瘤。多西紫杉醇（DTX）是一种用于治疗乳腺癌的紫杉烷类药物，属于 BCS 分类-IV 类化合物（口服生物利用度低、溶解度和肠道通透性低）。纳米技术策略可以通过促进药物持续释放和降低系统毒性来提高化疗效果。纳米结构脂质载体（NLC）将疏水性药物包裹在其混合脂质基质中，并且在储存过程中缺陷阻止药物排出。本工作描述了通过实验设计（2 因素设计）制备含有 Copaiba 油（CO）作为功能性赋形剂的新型 NLC 制剂。优化的制剂（NLC）显示出接近 100%的 DTX 包封效率，并通过不同的技术（DLS、NTA、TEM/FE-SEM、DSC 和 XRD）进行了表征，在 25°C 下储存 12 个月稳定。与商业 DTX（10 h）相比，CO 和 NLC 的药物释放时间延长至 54 h。体外细胞毒性试验表明，CO 和 NLC 具有抗增殖作用，可降低乳腺癌（4T1/MCF-7）和健康（NIH-3T3）细胞的细胞活力，效果优于商业 DTX。因此，NLC 作为一种有前途的药物递送系统，具有显著的抗癌作用（由 CO 增强）和持续释放，可以在较低的 DTX 剂量下降低系统毒性。
