Intraperitoneal administration of doxorubicin-encapsulated Brucea javanica oil nanoemulsion against malignant ascites

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-07-20 DOI:10.1016/j.ejpb.2024.114422
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Abstract

Malignant ascites is a common complication of advanced cancers, which reduces survival rates and diminishes patients’ quality of life. Intraperitoneal chemotherapy is a conventional method for treating cancer-related ascites, but the poor drug retention of conventional drugs requires frequent administration to maintain sustained anti-tumor effects. In this study, we encapsulated doxorubicin (DOX) into Brucea javanica oil (BJO) to develop a water-in-oil (W/O) nanoemulsion called BJO@DOX for the treatment of malignant ascites through in-situ intraperitoneal administration. BJO significantly induced apoptosis of S180 cells by upregulating the expression of p53 and caspase-3 (cleaved). Additionally, BJO notably downregulated the expression of Bcl-2, further promoting apoptosis of S180 cells. Cell apoptosis significantly inhibited ascites formation and tumor cell proliferation in a mouse model. The combination of DOX and BJO exhibited satisfactory synergistic effects, consequently prolonging the survival period of mice. Histological examination of major organs indicated that the nanoemulsion had excellent biosafety in vivo. The BJO@DOX nanoemulsion represents a promising platform for in-situ chemotherapy of malignant ascites.

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腹腔注射多柔比星包裹的Brucea javanica油纳米乳剂治疗恶性腹水。
恶性腹水是晚期癌症的常见并发症,会降低患者的生存率和生活质量。腹腔化疗是治疗癌症相关腹水的传统方法,但传统药物的药物保留性差,需要频繁给药才能维持持续的抗肿瘤效果。在这项研究中,我们将多柔比星(DOX)封装到布鲁斯油(BJO)中,开发出一种名为 BJO@DOX 的油包水(W/O)纳米乳液,通过腹腔内原位给药治疗恶性腹水。BJO 通过上调 p53 和 caspase-3 (裂解)的表达,明显诱导 S180 细胞凋亡。此外,BJO 还能明显下调 Bcl-2 的表达,进一步促进 S180 细胞的凋亡。在小鼠模型中,细胞凋亡明显抑制了腹水的形成和肿瘤细胞的增殖。DOX 和 BJO 的联合应用产生了令人满意的协同效应,从而延长了小鼠的生存期。主要器官的组织学检查表明,纳米乳液在体内具有良好的生物安全性。BJO@DOX 纳米乳液是一种用于恶性腹水原位化疗的前景广阔的平台。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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