RESUMEN
Breast and cervical cancers are the most common heterogeneous malignancies in women. Chemotherapy with conventional drug delivery systems having several limitations along with development of multidrug resistance compelled us to seek out targeted therapeutics. Nanoparticles are suitable substitutes to circumvent multidrug resistance for the targeted treatment of cancer. The current study was aimed to investigate the anticancer effect of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors. The average size of carvacrol-loaded chitosan nanoparticles was found to be 80 nm with 24.7 mV ζ-potential, and maximum absorbance was observed at 275 nm. Among all drug combinations, the carvacrol nanoparticles with the doxorubicin combination group exerted greater dose-dependent growth inhibition of both MCF-7 and HeLa cells as compared to single carvacrol nanoparticles and doxorubicin. Combination index values of carvacrol nanoparticles and the doxorubicin combination group showed a strong synergistic effect as they were found to be between 0.2 and 0.4, 0.31 for MCF-7 and 0.34 for HeLa cells. The carvacrol nanoparticles in combination with doxorubicin on MCF-7 cells reduced the dose 16.32-fold for carvacrol nanoparticles and 4.09-fold for doxorubicin at 6.23 µg/mL IC50, while on HeLa cells, this combination reduced the dose 13.18-fold for carvacrol nanoparticles and 3.83-fold for doxorubicin at 9.33 µg/mL IC50. As the dose reduction values were greater than 1, they indicated favorable dose reduction. It was concluded that the combination of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors may represent an innovative and promising strategy to improve the efficacy, resistance, and targeted delivery of chemotherapeutics in cancer.
RESUMEN
The increasing prevalence of antibiotic resistant bacteria is a significant healthcare crisis with substantial socioeconomic impact on global community. The development of new antibiotics is both costly and time-consuming prompting the exploration of alternative solutions such as nanotechnology which represents opportunities for targeted drug delivery and reduced MIC. However, concerns have arisen regarding genotoxic effects of nanoparticles on human health necessitating an evaluation of nanoparticle induced DNA damage. This study aimed to investigate the antibacterial potential of already prepared, characterized chitosan nanoparticles loaded with carvacrol and their potential synergism with Topoisomerase II inhibitors against S. aureus, E. coli and S. typhi using agar well diffusion, microdilution and checkerboard method. Genotoxicity was assessed through comet assay. Results showed that both alone and drug combinations of varying concentrations exhibited greater zones of inhibition at higher concentrations. Carvacrol nanoparticles combined with ciprofloxacin and doxorubicin significantly reduced MIC compared to the drugs used alone. The MIC50 values for ciprofloxacin were 35.8 µg/ml, 48.74 µg/ml, 35.57 µg/ml while doxorubicin showed MIC50 values of 20.79 µg/ml, 34.35 µg/ml, 25.32 µg/ml against S. aureus, E. coli and S. typhi respectively. The FICI of ciprofloxacin and doxorubicin with carvacrol nanoparticles found ≤ 0.5 Such as 0.44, 0.44,0.48 for ciprofloxacin and 0.45, 0.45, 0.46 for doxorubicin against S. aureus, E. coli and S. typhi respectively revealed the synergistic effect. The analysis of comet assay output images showed alteration of DNA at high concentrations. Our results suggested that carvacrol nanoparticles in combination with Topoisomerase inhibitors may prevent and control the emergence of resistant bacteria with reduced dose.
RESUMEN
The use of plants in disease treatment is cost effective and relatively safe. This study was designed to investigate anti-hyperlipidemic and anti-diabetic activity of ethanolic leaf extract of Catharanthus roseus alone and in combination therapy in hyperlipidemic & diabetic mice. Eight groups comprising five mice each were used. Group A was hyperlipidemic control, group B, C, D received atorvastatin (20 mg/kg), leaf extract (200 mg/kg) and leaf extract in combination with atorvastatin (200 mg/kg and 20 mg/kg) orally for 15 days. Group E was diabetic control. Group F, G, H received sitagliptin (40 mg/kg), leaf extract (200 mg/kg) and extract in combination with sitagliptin (200 mg/kg and 40 mg/kg) orally for 7 days. Blood cholesterol levels were measured at 1st, 5th, 10th and 15th day and fasting blood sugar levels were measured at 2, 12, 24, 72 and 168 hours during treatment. One-way ANOVA with tukey- kramer multiple comparison test was used. The chemical characterization of ethanolic extract of Catharanthus roseus leaves showed presence of alkaloids, saponins, tannins and flavonoids. Ethanolic extract of Catharanthus roseus has significant anti-hyperlipidemic & anti-diabetic effects (p<0.05, p<0.01) when compared with control but had not cause significantly increase in anti-hyperlipidemic effects of atorvastatin. While significantly increased the antidiabetic effect of sitagliptin (p<0.05)