多西紫杉醇（DTX）是一种有价值的抗肿瘤化疗药物，但口服生物利用度有限。本研究旨在使用从黄连提取物中提取的天然纳米颗粒（Nnps）开发一种有效的 DTX 口服给药系统。使用优化的热诱导策略创建了负载 DTX 的自组装纳米颗粒（Nnps-DTX）。 Nnps-DTX 的形状、大小、Zeta 电位和体外稳定性都经过仔细检查。此外，该研究还研究了 Nnps-DTX 中 DTX 的封装效率、负载能力、晶型和分子间相互作用。随后，系统评估了 Nnps-DTX 中 DTX 的溶解度、释放、细胞摄取、代谢稳定性和临床前药代动力学。最后，在三种肿瘤细胞系中评估了Nnps-DTX的细胞毒性。Nnps-DTX呈球形，大小138.6±8.2 nm，Zeta电位为-20.8±0.6 mV，DTX包封率为77.6±8.5 %，DTX 负载能力为 6.8 ± 1.9%。 Nnps-DTX 的形成涉及氢键、疏水相互作用和静电相互作用。 Nnps-DTX 中的 DTX 呈无定形形式，与游离 DTX 相比，溶解度和释放度提高（23.3 倍）。口服治疗后，Nnps-DTX组小鼠的门静脉、体循环、肝脏和肺中的DTX峰值浓度比DTX组小鼠高8.8、23.4、44.6和5.7倍。在 Caco-2 细胞中进行的实验表明，与游离 DTX 相比，Nnps-DTX 对 DTX 的摄取显着增加，而吲哚美辛（一种小凹介导的内吞作用抑制剂）可显着抑制这种吸收。此外，与 DTX 相比，Nnps-DTX 中的 DTX 在肝微粒体中表现出更好的代谢稳定性。值得注意的是，Nnps-DTX 显着降低了 MCF-7、HCT116 和 HepG2 细胞的活力。新型自组装纳米颗粒显着增强了口服 DTX 的细胞吸收、溶解度、释放、代谢稳定性和药代动力学，并表现出强大的抗肿瘤细胞毒性细胞系。© 2024 Ye 等人。

Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.© 2024 Ye et al.