BackgroundThe systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line.ResultsWe optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells.ConclusionsMost importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

An acidophilic and Ca(2+)-independent amylase was purified from a newly isolated Bacillus sp. DR90 by ion-exchange chromatography, and exhibited a molecular weight of 68.9 kDa by SDS-PAGE. The optimum pH and temperature of the enzyme were found to be 4.0 and 45 °C, respectively. The enzyme activity was increased by Ba(2+), Fe(2+) and Mg(2+), and decreased by Hg(2+) and Zn(2+), while it was not affected by Na(+), K(+), phenylmethylsulfonyl fluoride and β-mercaptoethanol. Ca(2+) and EDTA did not have significant effect on the enzyme activity and thermal stability. The values of K m and V max for starch as substrate were 4.5 ± 0.13 mg/ml and 307 ± 12 μM/min/mg, respectively. N,N-dialkylimidazolium-based ionic liquids such as 1-hexyl-3-methylimidazolium bromide [HMIM][Br] have inhibitory effect on the enzyme activity. Thin layer chromatography analyses displayed that maltose and glucose are the main products of the enzyme reaction on starch. Regarding the features of the enzyme, it may be utilized as a novel candidate for industrial applications.

Introduction: Ginsenoside Rh2, purified from the Panax ginseng root, has been demonstrated to possess anticancer properties against various cancerous cells including colorectal, breast, skin, ovarian, prostate, and liver cancerous cells. However, the poor bioavailability, low stability on gastrointestinal systems, and fast plasma elimination limit further clinical applications of Ginsenoside Rh2 for cancer treatments. In this study, a novel formulation of niosomal Ginsenoside Rh2 was prepared using the thin film hydration technique. Methods: The niosomal formulation contained Span 60 and cholesterol, and cationic lipid DOTAP was evaluated by determining particle size distribution, encapsulation efficiency, the polydispersity index (PDI), and surface morphology. The cytotoxic effects of free Ginsenoside Rh2 and Ginsenoside Rh2-loaded niosomes were determined using the MTT method in the PC3 prostate cancer cell line. For the investigation of the in vitro cellular uptake of Ginsenoside Rh2loaded niosome, two formulations were prepared: the Ginsenoside Rh2-loaded niosomal formula containing 5% DOTAP and the Ginsenoside Rh2-loaded niosomal formula without DOTAP. Results: The mean size, DPI, zeta potential, and encapsulation efficiency of the Ginsenoside Rh2-loaded nanoniosomal formulation containing DOTAP were 93.5±2.1 nm, 0.203±0.01, +4.65±0.65, and 98.32% ±2.4, respectively. The niosomal vesicles were found to be round and have a smooth surface. The release profile of Ginsenoside Rh2 from niosome was biphasic. Furthermore, a twofold reduction in the Ginsenoside Rh2 concentration was measured when Ginsenoside Rh2 was administered in a nanoniosomal form compared to free Ginsenoside Rh2 solutions in the PC3 prostate cancer cell line. After storage for 90 days, the encapsulation efficiency, vesicle size, PDI, and zeta potential of the optimized formulation did not significantly change compared to the freshly prepared samples. The cellular uptake experiments of the niosomal formulation demonstrated that by adding DOTAP to the niosomal formulation, the cellular uptake was enhanced. Discussion: The enhanced cellular uptake and cytotoxic activity of the Ginsenoside Rh2 nanoniosomal formulation on the PC3 cell make it an attractive candidate for application as a nano-sized delivery vehicle to transfer Ginsenoside Rh2 to cancer cells.

In this study, sarcotoxin Pd-functionalized graphene oxide (GO-Pd) was synthesized as a new condom-coating agent. Antimicrobial activity was evaluated by radial diffusion assay (RDA) and absorbance-based methods. Sperm motility and morphology were assessed in different concentrations of designed nanostructures. Peptide stability on the GO structures was assessed by the CD technique. GO-Pd showed the highest contact angle. The results approved that GO-Pd had broad-spectrum antimicrobial activities against examined pathogens, especially vaginal infections such as Candida vulvovaginitis. This antimicrobial activity was more than pristine peptides, vancomycin, and fluconazole. GO-Pd also had a higher inhibitory activity on the sperm motility and viability than pristine peptides. GO-Pd had high stability and activity in all examined conditions. But, naked peptides had low stability and activity after incubation in acidic pH and high temperatures (>38°C). In all tests, GO-Pd showed a significant difference compared to naked peptide. Based on the results, GO-Pd can be used as a condom coating to prevent unplanned pregnancy and sexually transmitted infections.

The combination therapy of cytotoxic drugs and chemosensitizing agents encapsulated in nanoparticles has been highlighted as an effective treatment for various cancers. Combination therapy is promising to produce synergistic anticancer effects, to magnify the treatment effect and overcome multidrug resistance. In this investigation, we have studied augmentation of therapeutic efficacy upon c combinational treatment of paclitaxel (PCL) and curcumin (Cur), an inhibitor of nuclear factor kappa B (NF-κB), in OVCAR-3 cell. PCL and Cur were encapsulated in nanoniosome formulations. Then, the effects of nanoniosome formulations on cytotoxicity, expression profile of AKT-1 gene and NF-κB activity were evaluated. The findings showed that nanoniosomes were highly efficient in delivering the PCL and Cur drugs to OVCAR-3 cell. A 3-fold and 3.6-fold reduction in Cur and PCL concentration were measured, respectively, when the Cur and PCL were administered in nanoniosomes compared to free Cur and free PCL solutions in OVCAR-3 cell. Moreover, curcumin could significantly increase cell growth inhibition of paclitaxel so that, in presence of NioCur, the IC50 of NioPCL was diminished to ∼2.4 –fold. AKT-1 gene expression studies showed that co-administration of curcumin/paclitaxel nanoniosome formulations caused 91.2% reduction in AKT-1 gene expression compared to control group. On the other hand, this co-administration caused 79.42% reduction in the amount of NF-κB activity and a 4-fold reduction in the activity of the MDR protein pumps in cancer cells compared to the control group. Our findings demonstrate that the combination therapy of PCL with Cur using the nanoniosomes delivery is a promising strategy for breast cancer more effective therapy