Preparation and characterization of brain-targeted polymeric nanocarriers (Frankincense-PMBN-lactoferrin) and in-vivo evaluation on an Alzheimer's disease-like rat model induced by scopolamine.

Experiments have demonstrated that frankincense may offer protection against scopolamine-induced Alzheimer's disease by mitigating cholinergic dysfunction and inhibiting inflammatory mediators. Nevertheless, its instability and limited water solubility lead to diminished medicinal efficacy. In this study, we utilized PMBN (poly [MPC-co-(BMA)-co-(MEONP)]) as a nanocarrier for targeted brain drug delivery of frankincense, employing lactoferrin as a ligand for precise targeting. Characterization of nanoparticle properties was conducted through FTIR and FESEM analysis, and the in-vitro drug release percentage from the nanoparticles was quantified. To induce Alzheimer's-like dementia in rats, scopolamine was intraperitoneally administered at a dose of 1 mg/kg/day for 14 days. Subsequently, behavioral assessments (Y-maze, passive avoidance test, tail suspension test) were performed, followed by evaluations of acetylcholinesterase (AChE), reduced glutathione (GSH), catalase (CAT), and brain histopathology at the conclusion of the treatment period. The results revealed that the nanoparticles had a size of 106.6 nm and a zeta potential of -3.8 mV. The maximum release of frankincense in the PBS environment from PMBN nanoparticles was 18.2 %, in accordance with the Peppas model. Behavioral tests indicated that targeted drug nanoparticles (F-PMBN-Lf) exhibited the capability to alleviate stress and depression while enhancing short-term memory in scopolamine-induced animals. Additionally, F-PMBN-Lf counteracted the scopolamine-induced elevation of AChE activity and GSH levels. However, it resulted in decreased activity of the antioxidant enzyme CAT compared to the scopolamine group. Histological analysis of brain tissue suggested that F-PMBN-Lf exerted a notable neuroprotective effect, preserving neuronal cells in contrast to the scopolamine-induced group. It appears that the polymer nanoparticles containing this plant extract have introduced a novel neuroprotective approach for the treatment of Alzheimer's disease.

Antioxidant activity and cytotoxicity of exopolysaccharide from mushroom Hericium coralloides in submerged fermentation.

Mushrooms of the genus Hericium spp. represent a series of delicious edible mushrooms with medicinal value. Here, for the first time, the species native to Iran, the mushroom Hericium coralloides, was collected in Mazandaran province, identified, and registered with the NCBI under accession number MW136052. The production of exopolysaccharides (EPS) in submerged culture was optimized using the response surface method. Among the physicochemical and culture medium conditions tested, rotation speed and concentration of maltose and peptone of soybean significantly affected the production of EPS. The proposed model predicts maximum EPS production (0.13 g/L) at 50 g/L maltose, 3 g/L soy peptone, and 1 g/L yeast extract, pH = 6.5, 200 rpm, inoculum at 5% v/v, and 22 °C. The molecular weight of the EPS chains was 413 and 1578 Da. EPS has antioxidant action (EC50 = 6.59 mg/mL) and cytotoxic activity against cancer cells. The viability of AGS and MKN-45 cancer cell lines declined to 20 and 30% after 48 h of the EPS treatment. H. coralloides EPS could be considered a natural dietary anti-cancer supplement. Further studies are necessary to understand the mechanism of the H. coralloides EPS activity on the cell cycle of cancer cells and to prove its action in vivo. Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-03386-0.

Design and development of chitosan-insulin-transfersomes (Transfersulin) as effective intranasal nanovesicles for the treatment of Alzheimer's disease: In vitro, in vivo, and ex vivo evaluations.

This study aimed to prepare and characterize chitosan-Transfersulin (CTI) as an effective intranasal drug delivery system (IDDS) for the treatment of memory disorders by mediating insulin (INS) transport into the brain. Tween 80 was used as an edge activator and chitosan (CS) to increase the elasticity of CTI. CTI nanovesicles were prepared by the film hydration method and characterized after optimization. Optimal values of particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading were found to be 137.9 ± 28.2 nm, 0.20, + 23.4 mV, 65.1 ± 0.9 %, and 9.1 ± 0.4 %, respectively. The TEM image supported these findings. FTIR and TGA also demonstrated suitable entrapment of INS in CTI without any chemical interaction. The circular dichroism and fluorescence spectroscopy results confirmed INS's stability and structural integrity released from the CTI. The nasal uptake of INS loaded into CTI was confirmed by optical fluorescence imaging. Histological inspections of the hippocampus also confirmed the results of the behavioral tests. In conclusion, these nanoformulations exhibited greater neuroprotective effects on rats via increased intracellular drug uptake and sustained retention, and it appears to be a promising and effective IDDS for treating Alzheimer's disease (AD).

The HbA1c and blood glucose response to selenium-rich polysaccharide from Fomes fomentarius loaded solid lipid nanoparticles as a potential antidiabetic agent in rats.

Fomes fomentarius is a medicinal fungus used in traditional Chinese medicine to treat various illnesses. Antidiabetic effects of F. fomentarius extracts have been reported recently. In this study, F. fomentarius extracellular polysaccharide (PS) was prepared, and then to enhance its antidiabetic effects, Na2SeO3 was added to the culture medium, and selenium-polysaccharide (PS-Se) was obtained. Also, solid lipid nanoparticles containing PS (SLN-PS) and PS-Se (SLN-PS-Se) were synthesized by the microemulsion method to compare their effects with free polysaccharides in streptozotocin (STZ) diabetic rats. Optimized SLNs had a size of 170.5 nm and drug loading of 9.27 %. EDS analysis confirmed that Se presence in PS-Se. Characterization analyses such as FTIR, DSC, TGA, and XRD suggested that SLNs have good thermal stability and crystalline nature. Release of PS from SLNs demonstrated sustained profile, and MTT assay proved that PSs and SLNs have no cytotoxicity. Furthermore, oral administration of PS, PS-Se, SLN-PS, and SLN-PS-Se for 28 days to diabetic rats significantly declined blood glucose by 48.24 %, 49.96 %, 55.50 %, and 60.47 %, respectively. Also, insulin secretion and body weight improved, and HbA1c levels decreased. Treatment by PS, PS-Se, SLN-PS, and SLN-PS-Se alleviated lipid profiles, liver enzymes, and serum proteins. Liver anti-oxidant parameters and histopathological observation of the liver, pancreas, and kidney confirmed that F. fomentarius PSs and SLNs have antidiabetic impacts. Moreover, supplementation of PS with selenium improves its anti-hyperglycemic effects. Finally, SLN-PS and SLN-PS-Se showed a higher antidiabetic impact than free PS and PS-Se.

Preparation, characterization, and in vivo evaluation of Rose damascene extract loaded solid lipid nanoparticles for targeted brain delivery.

According to a variety of experiments, Rose damascene may lead to memory enhancement and acetylcholine esterase inhibition. However, Rose damascene cannot pass through the blood-brain barrier due to its hydrophilic contents. Solid lipid nanoparticles (SLNs) are suitable carriers for brain drug delivery. Herein, SLNs were made by micro-emulsion method. Then, lactoferrin was covalently attached to the surface of the nanoparticles by amide bond interaction for targeted delivery. The nanoparticle properties and the amount of attached lactoferrin were calculated. The effect of the selected compounds on scopolamine-induced animals was also measured by Y-maze, passive avoidance test, elevated plus maze, and forced swim test. The results revealed that the size and zeta potential of nanoparticles were 52 nm and - 13 mV before conjugation, and 161 nm and - 16 mV after conjugation, respectively. The percentage of entrapment efficiency and drug loading before conjugation was 98 ,93.6 and, after conjugation, was 11.2, 15.9, respectively. According to Y-maze and passive avoidance test results, Rose damascene can enhance short-term memory and may also reduce anxiety and depression in scopolamine-induced animals.

Enhancement of exopolysaccharide production from Ganoderma lucidum using a novel submerged volatile co-culture system.

Based on the impact of volatile organic compounds (VOCs) on secondary metabolite pathways, a novel submerged volatile co-culture system was constructed, and the effects of thirteen fungal and bacterial VOCs were investigated on Ganoderma lucidum exopolysaccharides production. The results demonstrated at least a 2.2-fold increase in exopolysaccharide (EPS) specific production yield in 6 days submerged volatile co-culture of G. lucidum with Pleurotus ostreatus. Therefore, P. ostreatus was selected as a variable culture, and the effects of agitation speed, inoculum size, initial pH, and co-culture volume on EPSs production were investigated using a Taguchi L9 orthogonal array. Finally, the highest concentration of EPSs (3.35 ± 0.22 g L-1) was obtained under optimized conditions; initial pH 5.0, inoculum size 10%, 150 rpm, and 3:1 volume ratio of variable culture to main culture.

Effects of microbial volatile organic compounds on Ganoderma lucidum growth and ganoderic acids production in Co-v-cultures (volatile co-cultures).

Co-v-culture (co-cultivations of physically separated microbes that only interact through the air) systems were designed to investigate the effects of microbial volatile organic compounds (mVOCs) from about 20 different microbes, on a medicinal fungus, Ganoderma lucidum. For more accuracy in co-cultivations, a novel synchronized cultivation approach was tested for culturing G. lucidum. The hyphal growth of G. lucidum and the content of its ganoderic acids (GAs) were measured. In almost all of the co-v-cultures, there was an inhibiting effect on hyphal growth and a promoting effect on GAs contents. In inducing GAs production, Bacillus cereus PTCC 1247 and Pseudomonas aeruginosa UTMC 1404 were the most effective ones, as, compared to control cultures, GAs content increased 2.8 fold. Comparing different co-v-cultivations demonstrated that the concentrations of mVOCs, oxygen, and carbon dioxide were the main players in co-v-cultures. No correlation was found between hyphal growth and GAs production. Strains of the same species imposed totally different effects on hyphal growth or GAs production. This study has investigated the effects of mVOCs on G. lucidum for the first time. Moreover, it suggests that co-v-cultivation may be a promising biotechnological approach to improve the production in G. lucidum.

Electrospun Schizophyllan/polyvinyl alcohol blend nanofibrous scaffold as potential wound healing.

In this study, aqueous Schizophyllan (SPG) (1.5 w/v%) was mixed with aqueous polyvinyl alcohol (PVA) (10 w/v%) at various volume ratios and electrospun to prepare nanofibers. The fiber diameter was decreased by increasing the SPG content. A reliable linear relationship (p < 0.01) was established between the solution properties and fiber diameter. Contiguous, bead-free, and smooth fibers were obtained when the SPG/PVA ratios were 20:80, 30:70, and 40:60. FT-IR spectra, SEM images, tensile testing, swelling ratios, and water contact angle were utilized to characterize this glutaraldehyde (Glu) vapor cross-linked nanofibers in order to analyze the morphology, functional groups, mechanical attributes, hydrophilicity, and humidity of the nanofibers for skin tissue regeneration. Furthermore, the cell culture that was studied by the use of fibroblast (L929) cells showed that these SPG-based nanofibrous scaffolds could generate the improved cell adhesion. In conclusion, it was observed that SPG/PVA nanofiber mat in a volume ratio of 20:80 after 3 day was a suitable material for improving the wound healing, as it could increase cell proliferation and migration that possessed fiber diameter. The characteristics of this nanofiber were 267 nm, contact angle of 47.75°, good swelling behavior (289%), the ultimate strength of 6.513 MPa, Young modulus of 2.665 MPa, and cell viability of 150%.

In vivo anti-obesity efficacy of curcumin loaded nanofibers transdermal patches in high-fat diet induced obese rats.

Obesity as a dominant problem in developed countries which is known to be basic step of so many diseases is subjected to find a solution for in this work. Curcumin containing polyvinyl alcohol-gelatin nanofibers which ranging from 200 to 250 nm in diameter as a transdermal drug delivery system for declining volume of subcutaneous adipose tissue is investigated here. Morphology and synthesis method of nanofibers is designed and optimized by statistical software and a totally uniform and reproducible method of synthesis is used for preparation of a transdermal patch. Effectiveness of delivery system in transport of drug through skin is confirmed by side by side arrangement transdermal diffusion cells. This transdermal patch used for animal test showed 4 to 7% decrease in total amount of adipose tissue estimated by whole body magnetic resonance imaging technique.

Chitin and chitosan biopolymer production from the Iranian medicinal fungus Ganoderma lucidum: Optimization and characterization.

Chitin and chitosan with unique properties and numerous applications can be produced from fungus. The production of chitin and chitosan from the mycelia of an Iranian Ganoderma lucidum was studied to improve cell growth and chitin productivity. Inoculum size and initial pH as two effective variables on the growth of G. lucidum and chitin production were optimized using response surface method (RSM) by central composite design (CCD). The results verified the significant effect of these two variables on the cell growth and chitin production. In optimum conditions, including pH = 5.7 and inoculum size of 7.4%, the cell dry weight was 5.91 g/L and the amount of chitin production was 1.08 g/L with the productivity of 0.083 g/(L day). The produced chitin and chitosan were characterized using XRD and FTIR. Moreover, the antibacterial activity of the produced chitosan was investigated and compared with the commercial chitosan. The results showed that the produced chitin and chitosan had suitable quality and the Iranian G. lucidum would be a great source for safe and high-quality chitin and chitosan production.

Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles.

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood-brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6 nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.

Synthesis and Characterization of PMBN as A Biocompatible Nanopolymer for Bio-Applications.

OBJECTIVE: Poly [2-methacryloyloxyethyl phosphoryl choline (MPC)-co-n-buthyl methacrylate (BMA)-co-p-nitrophenyl-oxycrabonyl poly ethylene glycol-methacrylate (ME- ONP)] (PMBN), a biocompatible terpolymer, is a unique polymer with applications that range from drug delivery systems (DDS) to scaffolds and biomedical devices. In this research, we have prepared a monomer of p-nitrophenyl-oxycarbonyl poly (ethylene glycol) methacrylate (MEONP) to synthesize this polymer. Next, we designed and prepared a smart, water soluble, amphiphilic PMBN polymer composed of MPC, BMA, and MEONP. MATERIALS AND METHODS: In this experimental study, we dissolved MPC (4 mmol, 40% mole fraction), BMA (5 mmol, 50% mole fraction), and MEONP (1 mmol, 10% mole fraction) in 20 ml of dry ethanol in two necked flasks equipped with inlet-outlet gas. The structural characteristics of the synthesized monomer and polymer were determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (H-NMR), dynamic light scattering (DLS), gel permeation chromatography (GPC), scanning electron microscope (SEM), and transmission electron microscope (TEM) analyses for the first time. We treated the polymer with two different cell lines to determine its biocompatibility. RESULTS: FT-IR and H-NMR analyses confirmed the synthesis of the polymer. The size of polymer was approximately 40 nm with a molecular weight (MW) of 52 kDa, which would be excellent for a nano carrier. Microscopic analyses showed that the polymer was rodshaped. This polymer had no toxicity for individual cells. CONCLUSION: We report here, for the first time, the full properties of the PMBN polymer. The approximately 40 nm size with an acceptable zeta potential range of -8.47, PDI of 0.1, and rod-shaped structure indicated adequate parameters of a nanopolymer for nano bioapplications. We used this polymer to design a new smart nano carrier to treat leukemia stem cells based on a target DDS as a type of bio-application.

Production of nanocellulose in miniature-bioreactor: Optimization and characterization.

Bacterial cellulose (BC) is a very fascinating microbial biopolymer which is mainly produced by Gluconacetobacter xylinum. Optimization of BC production by G. xylinum was performed based on scale-down studies in miniature-bioreactor and response surface methodology in which the optimum pH value (6.5) and shaking rate (50 rpm) were obtained. The static culture condition for BC production has newly been defined. Nanostructure of BC includes nanofibers up to (60 nm) and nanoporosity up to (265 nm) was observed by scanning electron microscopy. By Fourier transform infrared spectroscopy study, the most expected BC interaction is nucleophilic interaction. MTT assay showed high biocompatibility. Appropriate mechanical strength (0.37 MPa) and Young's modulus (3.36 MPa) evinced BC scaffold utilization for skin tissue. The results indicate that BC sheets can be utilized in biomedical application and nanotechnology approaches.