据报道，乳腺癌是女性最常见的非皮肤恶性肿瘤之一。 Venetoclax (VEN) 是一种已批准用于治疗慢性粒细胞白血病的 BCl-2 抑制剂，口服生物利用度非常有限，但对乳腺癌具有巨大影响。在目前的研究中，设计和制造了装载维奈托克的自纳米乳化药物递送系统（VEN-SNEDDS），以提高VEN的水溶性、渗透性和抗癌功效。测定了重构的 SNEDDS 的各种表面活性参数，以检查所选表面活性剂混合物的性能。中央复合设计 (CCD) 用于优化 VEN-SNEDDS。重构的 VEN-SNEDDS 的球体尺寸为 71.3±2.8 nm，多分散指数为 0.113±0.01。与 MDA-MB-231、MCF-7 和 T47 D 细胞中的游离 VEN 相比，VEN-SNEDDS 的 IC50 分别降低约 3-4 倍、6-7 倍和 5-6 倍。与纯 VEN 相比，VEN-SNEDDS 在 MDA-MB-231 细胞中显示出更高的细胞摄取、细胞凋亡、活性氧生成以及更高的 BAX/BCL2 比率，同时降低了 MDA-MB-231 细胞中的 caspase 3 和 8 以及 BCL-2 水平。在体内药代动力学研究中，与 VEN 混悬液相比，VEN-SNEDDS 的 Cmax 大约提高了五倍，口服生物利用度也有所改善。© 2023。控释协会。

Breast cancer is reported as one of the most prevalent non-cutaneous malignancies in women. Venetoclax (VEN) is an approved BCl-2 inhibitor for the treatment of chronic myeloid leukemia with very limited oral bioavailability and exhibits an enormous impact on breast cancer. In the current investigation, venetoclax-loaded self-nanoemulsifying drug delivery systems (VEN-SNEDDS) were designed and fabricated to improve the aqueous solubility, permeability, and anticancer efficacy of VEN. Various surface-active parameters of the reconstituted SNEDDS were determined to scrutinize the performance of the selected surfactant mixture. Central composite design (CCD) was used to optimize the VEN-SNEDDS. The globule size of reconstituted VEN-SNEDDS was 71.3 ± 2.8 nm with a polydispersity index of 0.113 ± 0.01. VEN-SNEDDS displayed approximately 3-4 fold, 6-7 fold, and 5-6 fold reduced IC50 as compared to free VEN in MDA-MB-231, MCF-7, and T47 D cells, respectively. VEN-SNEDDS showed greater cellular uptake, apoptosis, reactive oxygen species generation, and higher BAX/BCL2 ratio with decreased caspase 3 and 8 and BCL-2 levels in the MDA-MB-231 cells compared to pure VEN. VEN-SNEDDS exhibited approximately fivefold enhancement in Cmax and an improved oral bioavailability compared to VEN suspension in in vivo pharmacokinetic studies.© 2023. Controlled Release Society.