In this work, a nano-in-micro carrier was constructed by loading polymer–lipid hybrid nanoparticles (NPs) into porous and hollow yeast cell wall microparticles (YPs) for macrophage-targeted oral delivery of cabazitaxel (CTX). The YPs, primarily composed of natural β-1,3-d-glucan, can be recognized by the apical membrane receptor, dectin-1, which has a high expression on macrophages and intestinal M cells. By combining electrostatic force-driven self-deposition with solvent hydration/lyophilization methods, the positively charged NPs loaded with CTX or fluorescence probes were efficiently packaged into YPs, as verified by scanning electron microscope (SEM), atomic force mircoscope (AFM), and confocal laser scanning microscopy (CLSM) images. NP-loaded YPs (NYPs) showed a slower in vitro drug release and higher drug stability compared with NPs in a simulated gastrointestinal environment. Biodistribution experiments confirmed a widespread distribution and extended retention time of NYPs in the intestinal tract after oral administration. Importantly, a large amount of NYPs were primarily accumulated and transported in the intestinal Peyer’s patches as visualized in distribution and absorption site studies, implying that NYPs were mainly absorbed through the lymphatic pathway. In vitro cell evaluation further demonstrated that NYPs were rapidly and efficiently taken up by macrophages via receptor dectin-1-mediated endocytosis using a mouse macrophage RAW 264.7 cell line. As expected, in the study of in vivo pharmacokinetics, the oral bioavailability of CTX was improved to 32.1% when loaded in NYPs, which is approximately 5.7 times higher than that of the CTX solution, indicating the NYPs are efficient for oral targeted delivery. Hence, this nano-in-micro carrier is believed to become a hopeful alternative strategy for increasing the oral absorption of small molecule drugs.

中文翻译：

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酵母细胞壁微粒中的纳米粒子的捕获为巨噬细胞靶向的卡巴他赛的口服。

在这项工作中，通过将聚合物-脂质杂化纳米颗粒（NPs）装入多孔和中空的酵母细胞壁微粒（YPs）中，以巨噬细胞为目标的卡巴他赛（CTX）口服递送，构建了纳米微载体。YPs主要由天然β-1,3- d组成-葡聚糖可被顶膜受体dectin-1识别，该蛋白在巨噬细胞和肠道M细胞中具有高表达。通过将静电力驱动的自沉积与溶剂水化/冻干方法相结合，负载了CTX或荧光探针的带正电荷的NP被有效地包装到YP中，这已通过扫描电子显微镜（SEM），原子力显微镜（AFM）和共聚焦激光扫描显微镜（CLSM）图像。在模拟胃肠道环境中，NP加载的YP（NYPs）与NPs相比，在体外的药物释放较慢，并且具有较高的药物稳定性。生物分布实验证实，口服后，NYP在肠道中分布广泛，保留时间延长。重要的，如分布和吸收部位研究所示，大量NYP主要在肠道Peyer斑块中积累和运输，这表明NYP主要通过淋巴途径吸收。体外细胞评估进一步证明，使用小鼠巨噬细胞RAW 264.7细胞系，巨噬细胞可通过受体dectin-1介导的内吞作用迅速有效地吸收NYP。正如预期的那样，在体内药代动力学研究中，将CTX装入NYP时的口服生物利用度提高到32.1％，约为CTX溶液的5.7倍，表明NYP对于口服靶向递送是有效的。因此，据信这种纳米微载体成为增加小分子药物口服吸收的一种有希望的替代策略。