RESUMEN
Combination chemotherapy has become a treatment modality for breast cancer. However, serious side effects and high cytotoxicity associated with this combination therapy make it a high-risk method for breast cancer treatment. This study evaluated the anticancer effect of decorated niosomal nanocarriers loaded with cisplatin (CIS) and epirubicin (EPI) in vitro (on SKBR3 and 4T1 breast cancer cells) and in vivo on BALB/c mice. For this purpose, polyethylene glycol (PEG) and folic acid (FA) were employed to prepare a functionalized niosomal system to improve endocytosis. FA-PEGylated niosomes exhibited desired encapsulation efficiencies of â¼91.2 and 71.9% for CIS and EPI, respectively. Moreover, cellular assays disclosed that a CIS and EPI-loaded niosome (NCE) and FA-PEGylated niosomal CIS and EPI (FPNCE) enhanced the apoptosis rate and cell migration in SKBR3 and 4T1 cells compared to CIS, EPI, and their combination (CIS+EPI). For FPNCE and NCE groups, the expression levels of Bax, Caspase3, Caspase9, and Mfn1 genes increased, whereas the expression of Bcl2, Drp1, MMP-2, and MMP-9 genes was downregulated. Histopathology results showed a reduction in the mitosis index, invasion, and pleomorphism in BALB/c inbred mice with NCE and FPNCE treatment. In this paper, for the first time, we report a niosomal nanocarrier functionalized with PEG and FA for codelivery of CIS and EPI to treat breast cancer. The results demonstrated that the codelivery of CIS and EPI through FA-PEGylated niosomes holds great potential for breast cancer treatment.
Asunto(s)
Cisplatino , Neoplasias , Animales , Línea Celular Tumoral , Cisplatino/farmacología , Epirrubicina/farmacología , Ácido Fólico/uso terapéutico , Concentración de Iones de Hidrógeno , Liposomas/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Neoplasias/tratamiento farmacológico , PolietilenglicolesRESUMEN
In the current study, for the first time, the synergistic activity of curcumin and silver/copper nanoparticles (NPs) was studied against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, a unique combination of curcumin and silver/copper NPs in free and encapsulated forms was prepared and delivered through a niosomal system. For this purpose, different niosomal formulations of curcumin and metal NPs were prepared by thin film hydration method. Then, the dual drug-loaded niosomes were dispersed in chitosan hydrogel in order to widen its applications. The effect of the molar ratios of lipid to drug and surfactant to cholesterol was investigated to find the optimized noisomal nanoparticles in terms of size, polydispersity index (PDI), and entrapment efficiency (EE). The size and PDI values were measured by dynamic light scattering (DLS). Morphology and in vitro drug release kinetics of niosomes were examined by scanning and transmission electron microscopy (SEM, TEM) and dialysis method, respectively. The drug-loaded niosomes and their hydrogel counterpart were screened for investigating their antibacterial activity against S. aureus and P. aeruginosa by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Furthermore, anti-biofilm assay and expression of biofilm-associated genes by Real-time PCR were performed to evaluate the anti-biofilm effect of NPs. In this study, the drug-loaded niosomal formulations showed good entrapment efficiencies (EE) with a sustained release profile over 72 h. Moreover, compared to free drugs, the optimized niosomal formulations increased antibacterial activity against the bacteria via promotion in the inhibition zone and reduction in MIC and MBC values. Interestingly, gel-based niosomal formulations increased the inhibition zone by about 6 mm and significantly decreased MIC and MBC values compared to niosomal formulations. Also, biofilm eradication of curcumin-metal NPs encapsulated into niosomal hydrogel was highest compared to free and niosomal drugs. Overall, curcumin-Cu or curcumin-Ag nanoparticle loaded niosomes incorporated in hydrogel hold great promise for biomedical applications.