ABSTRACT
All active natural molecules are not fully exploited as therapeutic agents, causing delays in the advancement of anticancer drug discovery. Viridiflorol is a natural volatile element that may work as anti-cancer compound. We tested the anticancer properties of viridiflorol at different concentrations ranging from 0.03 to 300 µM in vitro on three cancer cells including breast (MCF-7), lung (A549) and brain (Daoy). The cancer cells responses were documented after treatment using MTT and Annexin V assays. Viridiflorol showed cytotoxic effects against all tested cell lines, reducing cell viability in a concentration-dependent manner with variable IC50 values. Daoy and A549 cell lines were more sensitive to viridiflorol when compared with temozolomide and doxorubicin, respectively. Viridiflorol demonstrated the highest anticancer activity against the Daoy cells with an estimated IC50 of 0.1 µM followed by MCF-7 at 10 µM, and A549 at 30 µM. In addition, upon exposure to concentrations ranging from 30 µM to 300 µM of viridiflorol, early and late apoptotic cell death was induced in a concentration dependent manner in Daoy (55.8%-72.1%), MCF-7 (36.2%-72.7%) and A459 (35%-98.9%) cell lines, respectively. In conclusion, viridiflorol demonstrates cytotoxic and apoptotic ability in three different cancer cell lines (brain, breast and lung).
ABSTRACT
The antibacterial activity and biofilm reduction capability of liposome formulations encapsulating tobramycin (TL), and Tobramycin-N-acetylcysteine (TNL) were tested against tobramycin-resistant strains of E. coli, K. pneumoniae and A. baumannii in the presence of several resistant genes. All antibacterial activity were assessed against tobramycin-resistant bacterial clinical isolate strains, which were fully characterized by whole-genome sequencing (WGS). All isolates acquired one or more of AMEs genes, efflux pump genes, OMP genes, and biofilm formation genes. TL formulation inhibited the growth of EC_089 and KP_002 isolates from 64 mg/L and 1024 mg/L to 8 mg/L. TNL formulation reduced the MIC of the same isolates to 16 mg/L. TNL formulation was the only effective formulation against all A. baumannii strains compared with TL and conventional tobramycin (in the plektonic environment). Biofilm reduction was significantly observed when TL and TNL formulations were used against E. coli and K. pneumoniae strains. TNL formulation reduced biofilm formation at a low concentration of 16 mg/L compared with TL and conventional tobramycin. In conclusion, TL and TNL formulations particularly need to be tested on animal models, where they may pave the way to considering drug delivery for the treatment of serious infectious diseases.
ABSTRACT
E. coli is an Enterobacteriaceae that could develop resistance to various antibiotics and become a multi-drug resistant (MDR) bacterium. Options for treating MDR E. coli are limited and the pipeline is somewhat dry when it comes to antibiotics for MDR bacteria, so we aimed to explore more options to help in treating MDR E. coli. The purpose of this study is to examine the synergistic effect of a liposomal formulations of co-encapsulated azithromycin and N-acetylcysteine against E. coli. Liposomal azithromycin (LA) and liposomal azithromycin/N-acetylcysteine (LAN) were compared to free azithromycin. A broth dilution was used to measure the MIC and MBC of both formulations. The biofilm reduction activity, thermal stability measurements, stability studies, and cell toxicity analysis were performed. LA and LAN effectively reduced the MIC of E. coli SA10 strain, to 3 µg/ml and 2.5 µg/ml respectively. LAN at 1 × MIC recorded a 93.22% effectiveness in reducing an E. coli SA10 biofilm. The LA and LAN formulations were also structurally stable to 212 ± 2 °C and 198 ± 3 °C, respectively. In biological conditions, the formulations were largely stable in PBS conditions; however, they illustrated limited stability in sputum and plasma. We conclude that the formulation presented could be a promising therapy for E. coli resistance circumstances, providing the stability conditions have been enhanced.
ABSTRACT
Ciprofloxacin (CIP), a widely used antibiotic, is a poor biopharmaceutical resulting in low bioavailability. We optimized a CIP polymer-lipid hybrid nanoparticle (CIP-PLN) delivery system to enhance its biopharmaceutical attributes and the overall therapeutic performance. CIP-PLN formulations were prepared by a direct emulsification-solvent-evaporation method. Varying the type and ratio of lipid was tried to optimize a CIP-PLN formulation. All the prepared formulations were evaluated for their particle size, polydispersity index, zeta potential, physical stability, and drug entrapment efficiency. The drug in vitro release profile was also studied. Antibacterial activities were tested by the agar diffusion method for all CIP-PLN formulations against an Escherichia coli clinical bacterial isolate (EC04). CIP-PLN formulations showed average sizes in the range of 133.9 ± 1.7 nm to 217.1 ± 0.8 nm, exhibiting high size uniformity as indicated by polydispersity indices lower than 0.25. The entrapment efficiency was close to 80% for all formulations. The differential scanning calorimetry (DSC) thermograms indicated the existence of CIP in the amorphous state in all PLN formulations. Fourier transform infrared spectra indicated deep incorporation of molecular CIP within the polymer matrix. The release profile of CIP from PLN formulas showed a uniform prolonged drug profile, extended for a week from most formulations with a zero-order kinetics. The antibacterial activity of CIP-PLN formulations showed significantly higher antibacterial activity only with F4 containing lecithin as the lipid component. In conclusion, we successfully optimized a CIP-PLN formulation with a low nanoparticle size in a close range, high percentage of entrapment efficiency and drug loading, uniform prolonged release rate, and higher antibacterial activity against the EC04 clinical isolate.
