| Abstrakt: |
The objective of this study was to develop a nanoformulation of 5-fluorouracil (5-FU) combined with Andrographolide (AG) to synergize their anticancer activity, reduce the dose of 5-FU, and minimize the side effects of 5-FU. Solid lipid nanoparticles (SLNs) of 5-FU and AG were synthesized and characterized separately for average particle size, EE, DL, TEM, DSC, and FTIR. In vitro cytotoxicity was assessed in A549 lung cancer cells, and in vivo experiments were conducted using Ehrlich Ascites Carcinoma (EAC)-induced tumors in Balb/c mice, evaluating tumor regression parameters (TRP) and lifespan analysis (LSA). The average particle size of the SLNs was below 150 nm. The combination nanoformulation of AG and 5-FU exhibited enhanced cytotoxicity in A549 cell lines, with an IC50 value of 18.45 ± 1.03 (p < 0.05). In the in vivo study, the combination nanoformulation showed a decrease in tumor size, an increase in mean survival time, and a significant increment in lifespan compared to the toxic control and AG-SLNs treated groups (p < 0.05). These effects were almost comparable to those observed in the 5-FU-treated group. The combination of nanoformulations, AG, at a dose of 10 mg/kg body weight and 5-FU at 10 mg/kg body weight, demonstrated a synergistic anticancer effect, reduced dose of 5-FU, improved aqueous solubility of both drugs, and increased oral bioavailability. Additionally, nanoparticles were almost found to be stable and they showed potential for reducing side effects such as anemia or myelosuppression. These findings support the potential of combining AG-based chemotherapy with 5-FU for effective cancer prevention and treatment. Figure showing schematic diagram representing research work performed in this study. Abbreviations: SLN, solid-lipid nanoparticles; TEM, transmission electron microscopy; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared spectroscopy. [ABSTRACT FROM AUTHOR] |
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