In vitro and in silico evaluation of the design of nano-phyto-drug candidate for oral use against Staphylococcus aureus.

Onopordum acanthium is a medicinal plant with many important properties, such as antibacterial, anticancer, and anti-hypotensive properties. Although various studies reported the biological activities of O. acanthium, there is no study on its nano-phyto-drug formulation. The aim of this study is to develop a candidate nano-drug based on phytotherapeutic constituents and evaluate its efficiency in vitro and in silico. In this context, poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of O. acanthium extract (OAE) were synthesized and characterized. It was determined that the average particle size of OAE-PLGA-NPs was 214.9 ± 6.77 nm, and the zeta potential was -8.03 ± 0.85 mV, and PdI value was 0.064 ± 0.013. The encapsulation efficiency of OAE-PLGA-NPs was calculated as 91%, and the loading capacity as 75.83%. The in vitro drug release study showed that OAE was released from the PLGA NPs with 99.39% over the 6 days. Furthermore, the mutagenic and cytotoxic activity of free OAE and OAE-PLGA-NPs were evaluated by the Ames test and MTT test, respectively. Although 0.75 and 0.37 mg/mL free OAE concentrations caused both frameshift mutation and base pair substitution (p < 0.05), the administered OAE-PLGA NP concentrations were not mutagenic. It was determined with the MTT analysis that the doses of 0.75 and 1.5 mg/mL of free OAE had a cytotoxic effect on the L929 fibroblast cell line (p < 0.05), and OAE-PLGA-NPs had no cytotoxic effect. Moreover, the interaction between the OAE and S. aureus was also investigated using the molecular docking analysis method. The molecular docking and molecular dynamics (MD) results were implemented to elucidate the S. aureus MurE inhibition potential of OAE. It was shown that quercetin in the OAE content interacted significantly with the substantial residues in the catalytic pocket of the S. aureus MurE enzyme, and quercetin performed four hydrogen bond interactions corresponding to a low binding energy of -6.77 kcal/mol with catalytic pocket binding residues, which are crucial for the inhibition mechanism of S. aureus MurE. Finally, the bacterial inhibition values of free OAE and OAE-PLGA NPs were determined against S. aureus using a microdilution method. The antibacterial results showed that the inhibition value of the OAE-PLGA NPs was 69%. In conclusion, from the in vitro and in silico results of the nano-sized OAE-PLGA NP formulation produced in this study, it was evaluated that the formulation may be recommended as a safe and effective nano-phyto-drug candidate against S. aureus.

Laurus nobilis L. Essential Oil-Loaded PLGA as a Nanoformulation Candidate for Cancer Treatment.

The aim of this study was to obtain essential oil (LNEO) from the Laurus nobilis L. plant, and to prepare LNEO-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) as an approach in cancer treatment. The components of the obtained LNEO were analyzed using GC-MS. The LNEO-NPs were synthesized by the single-emulsion method. The LNEO-NPs were characterized using UV-Vis spectrometry, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and a DNA binding assay, which was performed via the UV-Vis titration method. According to the results, the LNEO-NPs had a 211.4 ± 4.031 nm average particle size, 0.068 ± 0.016 PdI, and -7.87 ± 1.15 mV zeta potential. The encapsulation efficiency and loading capacity were calculated as 59.25% and 25.65%, respectively, and the in vitro drug release study showed an LNEO release of 93.97 ± 3.78% over the 72 h period. Moreover, the LNEO was intercalatively bound to CT-DNA. In addition, the mechanism of action of LNEO on a dual PI3K/mTOR inhibitor was predicted, and its antiproliferative activity and mechanism were determined using molecular docking analysis. It was concluded that LNEO-loaded PLGA NPs may be used for cancer treatment as a novel phytotherapeutic agent-based controlled-release system.

Synthesis, characterization, biological activities and molecular docking of Epilobium parviflorum aqueous extract loaded chitosan nanoparticles.

Epilobium is a medicinal plant; its extracts are widely used traditional medicine due to their broad range of pharmacological and therapeutic properties. Its most prominent feature is its therapeutic effects on prostatic diseases. The aim of this study is preparation of controlled release system of Epilobium parviflorum, and determination of its potential of anticancer applications. For this purpose, Epilobium parviflorum extract (EPE) loaded chitosan nanoparticles were prepared with ionic gelation method to increase the bioavailability of the extract. The nanoparticles were investigated in terms of size, zeta potential, polydispersity index, encapsulation efficiency, loading capacity and release profile. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the nanoparticles. Moreover, Ames/Salmonella test was used to determine the mutagenicity of EPE, and it was shown that it had no mutagenic effect. It was found that EPE loaded chitosan nanoparticles were with 64.47 nm in average size, 0.168 PdI and 15.2 mV zeta potential. Encapsulation efficiency and loading capacity were found as 92.46% and 8%, respectively. Finally, DNA binding assay and in silico molecular docking studies were performed between EPE and DNA in order to contribute to design of plant based controlled release system for use in cancer therapy.