Improving cisplatin chemotherapy in vivo by niosomal propolis and chrysin as nanoadjuvants

Breast cancer remains the most prevalent malignancy among women worldwide, with its incidence steadily increasing. Cisplatin (Cis) is a widely used chemotherapeutic drug. Natural compounds such as propolis and chrysin may help mitigate the toxic side effects of Cis while enhancing its therapeutic efficacy. This study aimed to evaluate the anticancer potential of ethanolic extract of propolis (EEP) and chrysin (Chry) through niosomal encapsulation (Nio). The synergistic effects of Nio formulations in combination with low-dose Cis were also investigated in vivo. EEP was extracted and analyzed for its phytochemical composition using gas chromatography-mass spectrometry (GC-MS). Both EEP and Chry were loaded onto niosomes, which were then characterized by transmission electron microscopy (TEM), dynamic light scattering, zeta potential, UV-Vis, and FTIR spectroscopy. Fifty adult female Swiss Albino mice were induced with Ehrlich carcinoma and randomly divided into ten treatment groups: control, Free Nio, Free EEP, Free Chry, Nio + EEP, Nio + Chry, Nio + EEP + low Cis, Nio + Chry + low Cis, low Cis, and high Cis groups. Treatments were administered intraperitoneally every three days. The study assessed the efficacy of cancer treatments by analyzing tumor histology, tracking growth, and tracking oxidative stress. In addition, the cytotoxicity of kidney and liver tissues was studied. Niosomes improved and enhanced the stability and encapsulation efficiency of EEP and Chry (90%). Combination treatments reduced tumor volume by about 90% compared to the control group and enhanced antioxidant activity. Histopathological evaluation of tumor tissue revealed that Nio + EEP + low Cis and Nio + Chry + low Cis significantly reduced mitotic figures and increased necrotic changes relative to the low and high cis groups. In the liver, these groups exhibited only mild necrobiotic changes and minimal vascular congestion, indicating a protective effect against cisplatin-induced hepatotoxicity. In the kidney, mild interstitial nephritis, limited tubular degeneration, and reduced glomerular hypercellularity were observed. EEP and Chry-loaded niosomes effectively enhanced the antitumor efficacy of low-dose cisplatin while minimizing systemic toxicity. These findings suggest that Nio-based natural adjuvants could be promising nanocarriers for combination cancer therapy.