Synergistic activity of crocin and crocin loaded in niosomes alone and in combination with fluconazole against Candida albicans isolates: In vitro and in silico study.

INTRODUCTION: Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates. MATERIAL AND METHODS: NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties. RESULTS: NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase. CONCLUSION: The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.

Chitosan-sialic acid nanoparticles of selenium: Statistical optimization of production, characterization, and assessment of cytotoxic effects against two human glioblastoma cell lines.

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs.

The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism.

In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism at gestational day (GD) 12.5 (600 mg/kg). Male offsprings were injected with EPO and NEPO in a clinically proper postnatal dosing regimen on postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of the first month. Then animals were sacrificed, and neuron morphology and KCC2 expression were examined by Nissl staining and Western blot. According to our findings, high-dose NEPO improved autism-associated phenotypes. Neuroprotective effects of EPO and NEPO have been shown in the hippocampus. Postnatal NEPO treatment reversed KCC2 expression abnormalities induced by prenatal VPA. Our results might support the role of KCC2 in ASD and the excitatory/inhibitory imbalance hypothesis. We suggested Nano- erythropoietin and other KCC2 interventions as a new approach to the early treatment and prevention of autism.

Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study.

Diabetes mellitus is one of the most common metabolic disorders. One of the important metabolic complications in diabetes is diabetic foot ulcer syndrome, which causes delayed and abnormal healing of the wound. The formulation of nanoscaffolds containing cod liver oil by altering the hemodynamic balance toward the vasodilators state, increasing wound blood supply, and altering plasma membrane properties, namely altering the membrane phospholipids composition, can be effective in wound healing. In this study, electrospinning method was used to produce poly lactic acid/chitosan nanoscaffolds as a suitable bio-substitute. After preparing the nanoscaffolds, the products were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Also optical properties of polymer and comparison between adsorption between single polymer and polymer-drug calculated with UV-Vis spectra. The structure and functional groups of the final products were characterized by Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive spectroscopy (EDAX) as elemental analysis. The results showed that the optimum formulation of cod liver oil was 30%, which formed a very thin fiber that rapidly absorbed to the wound and produced significant healing effects. According to the results, poly lactic acid/chitosan nanoscaffolds containing cod liver oil can be a suitable bio-product to be used in treating the diabetic foot ulcer syndrome.

A systematic study and effect of PLA/Al2O3 nanoscaffolds as dental resins: mechanochemical properties.

One of the major and important challenges in dental composite resin and restoration is the mechanical performance and property of materials. Nanotechnology can produce nanoscale materials that are used in dentistry to help stabilize and strengthen the dentistry. In this work, we study the synthesis and characterization of PLA/Al2O3 nanoscaffold in different conditions such as concentration, temperature, pH, microwave power and irradiation time. PLA/Al2O3 nanoscaffolds were prepared by a micelle-assisted hydrothermal method. Durability, stability and biodegradable nature of nanopolymers have created the much-applied potential for using this structures in many fields such as dental resin composites. Products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transition electron microscopy (TEM), Fourier transformed infrared spectrum (FT-IR), Dynamic light scattering (DLS) and atomic force microscopy (AFM). The synthesis factors were designed by Taguchi technique to control the process systematically. It was found that the intermolecular crosslinks between PLA and Al2O3 nanoparticles cause significant improves in the mechanical properties of PLA/Al2O3 nanoscaffold as dental nanocomposites. The flexural strength (88.0 MPa), modulus (7.5 GPa) and compressive strength (157.2 MPa) were calculated for PLA/Al2O3 nanoscaffolds loaded in Heliomolar Flow composite resins at 80 ppm (wt) concentration.