Intraperitoneal administration of doxorubicin-encapsulated Brucea javanica oil nanoemulsion against malignant ascites.
Jie DaiRenjin ChenJie WangPing ZhouBiqiong WangJianmei LiYun LuXianlun PangShaozhi FuPublished in: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (2024)
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.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- cell free
- oxidative stress
- signaling pathway
- cell proliferation
- cell cycle arrest
- poor prognosis
- mouse model
- cell death
- end stage renal disease
- pi k akt
- cancer therapy
- fatty acid
- newly diagnosed
- chronic kidney disease
- metabolic syndrome
- ejection fraction
- prognostic factors
- squamous cell carcinoma
- type diabetes
- emergency department
- peritoneal dialysis
- skeletal muscle
- free survival
- long non coding rna
- combination therapy
- smoking cessation
- high fat diet induced
- patient reported