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Abstract The role of Streptococcus mutans in the initiation of caries is related to its acidogenicity, aciduricity, and polysaccharides extracellular layer production by glucosyltransferases in dental biofilms. Therefore, inhibition of glucosyltransferase activity impairs the virulence of cariogenic biofilms, which can be used to prevent dental caries. We evaluated the anti-bacterial, anti-biofilm, and anti-glucosyltransferases effects of nanoliposomal herbal aqueous extracts of Liquorice (Glycyrrhiza glabra; G. glabra), Ginger (Zingiber officinale; Z. officinale), Pomegranate (Punica granatum; P. granatum), and Rose (Rosa damascene; R. damascene) via minimum bactericidal concentration and minimum inhibitory concentration against Streptococcus mutans strain ATCC 35,668. An anti-biofilm assay was performed using a minimum biofilm inhibitory concentration test. Among herbs, only P. granatum showed an antibacterial effect. Therefore, a nanoliposomal formulation of P. granatum was developed and characterized. Its effect on S.mutans glucosyltransferases was assessed by measuring glucan amount. The nanoliposomal formulation of P.granatum showed a significantly higher anti-biofilm effect than P. granatum aqueous extract. Their similar potential in blocking glucosyltransferases showed that the nanoliposomal formulation of P.granatum blocked other pathways rather than blocking glucosyltransferases for its anti-biofilm effect. Collectively, the nanoliposomal formulation of P.granatum, due to its anti- Streptococcus mutans characteristics, would be a production which open a new horizon for the oral pharmaceutical industry.

Abstract The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer.

Abstract Recently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15–313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat–Jouyban–Acree > Van’t Hoff–Jouyban–Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van’t Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA

This work is aimed to assess the effect of ultrasonic pre-treatment on the enzymatic hydrolysis of zein and the nanoencapsulation of vitamin D3 (VitD3) by zein hydrolysates (ZH). The ultrasonic pre-treatment significantly increased the degree of hydrolysis by and the α-helix, β-sheet, β-turns contents, and random coils were enhanced by ultrasonic pre-treatment. VitD3 was successfully encapsulated by the developed ZH nanoparticles (NPs), with an encapsulation efficiency of 95.23 ± 1.78 %. The surface charge and particle size of the nanoparticles (NPs) were −5.45 ± 1.76 mV and 39.43 ± 7.96 nm, respectively. The detailed morphology study of NPs showed a regular spherical morphology, and the chemical structures of NPs were characterized by Fourier Transform Infrared Red spectroscopy. Additionally, the developed NPs were added to milk, which exhibited high stability after one month of storage. In conclusion, the VitD3-loaded ZHNPs had considerable potential for fortifying different foodstuffs.

The primary aim of this study was to develop biocomposite films using carboxymethyl cellulose (CMC) (1 % w/v), okra mucilage (OM) (1–3 % w/v), and black cumin seed oil (BSO) (0–0.5 % v/v), based on the central composite design. The effects of OM and BSO concentrations on the properties of biocomposite films were evaluated using response surface methodology. Statistical analysis showed that all variables significantly contribute to the model (p < 0.05). The findings indicated that higher BSO concentrations considerably decreased (p < 0.05) the water vapor and oxygen permeability, moisture content, swelling factor, and water solubility of the produced films. Conversely, a rise in OM concentration notably increased (p < 0.05) the physical and barrier properties of the films. It was determined that an increase in OM concentration led to a decrease in tensile strength (TS), while the elongation at break (%EB) increased significantly (p < 0.05). Conversely, higher concentrations of BSO significantly improved both the TS and %EB values (p < 0.05). FE-SEM analysis revealed that for all films, microstructural irregularities increased with higher concentrations of OM and BSO. The formulation containing 1.82 % OM and 0.5 % BSO was identified as an optimal composition. FE-SEM and AFM analyses showed that the optimal film had higher microstructural discontinuity and surface roughness than the control film. The optimal film exhibited significantly higher antioxidant activity (p < 0.05) compared to the control film. Furthermore, FTIR analysis highlighted the presence of new intermolecular interactions within the functional groups of the optimal film’s matrix. Moreover, the optimal film demonstrated a higher melting temperature and a more amorphous structure than the control film. In conclusion, the optimized CMC/OM/BSO film presents promising potential for use in edible packaging.

Objectives: This study aimed to report a simple environmentally compatible method that is economically affordable for the facile biosynthesis of stable silver nanoparticles (AgNPs) in corn steep liquor (CSL) nutrient using the sewage of a leather factory. Materials and Methods: The biosynthesis of AgNPs were done by reduction of AgNO3 in the sewage of leather factory as a mixed bacterial culture and corn steep liquor under anaerobic condition while protecting from light. Results: The AgNPs were found to have a characteristic absorption peak at 416 nm on the ultraviolet-visible spectrum. Characterization of AgNPs was performed by x-ray diffraction (XRD) and Fourier-transform infrared (FTIR). The scanning electron microscopy (SEM) and transmission electron microscopes (TEM) images showed poly-dispersed spherical stable AgNPs with a maximum diameter of 20 nm. Moreover, the dynamic light scattering (DLS) showed that the average size of AgNPs was 15.57 nm with a zeta potential value of -19.2 mV. The synthesized nanoparticles demonstrated more antibacterial activity in opposition to gram-negative bacteria. The zone of inhibition of biosynthesized AgNPs in 1 mM concentration of AgNO3 against Escherichia coli was equal to that of gentamicin. Conclusions: The interaction of protein residues with AgNPs was identified, supporting that the proteins not only act as a reducing agent but also as a capping. The synthesized AgNPs showed antibacterial activity, providing commercial viability in biomedicine.

Background: Emulsion-based formulations have gained attention in food and pharmaceutical products due to their unique properties. However, their use in food product formulation faces problems because of phase separation and fat oxidation, which seriously reduces the quality of the product. Therefore, finding ways to increase the physical and oxidative stability of emulsions is valuable. This work aimed to assess of physicochemical properties of sodium caseinate (SC)-tannic acid (TA) complex treated with heating and ultrasonication as well as their efficiency in physical and oxidative stability of high internal phase Pickering emulsion (HIPPEs) as antioxidant colloidal particles. Methods: SC 1% (w/v) was mixed with a different concentration of TA (0.1, 0.3, 0.5, 0.7, 1% w/v) and the pH of solutions was adjusted to 9. The unheated, heat-treated, and ultrasonicated SC-TA complexes were analyzed to elucidate possible interaction using FTIR, fluorescence spectroscopy, and DSC. Finally, HIPPEs were prepared by mixing the prepared samples and soybean oil at a volume ratio of 25:75 v/v respectively. The microstructure of the most stable HIPPEs was assessed using SEM. Results: Based on the FTIR results the covalent bond in heat-treated SC-TA was formed via the Maillard reaction. In addition, the reduction of free amino groups confirms Schiff base formation. All treated SC-TA samples showed a superior ability to stabilize emulsion in comparison with native SC when used as an aqueous phase of HIPPEs. The long-term physical was observed in heat-treated SC-TA HIPPEs for over two months. In PEs stabilized by SC-TA complex nanoparticles, primary and secondary oxidation product levels were significantly lower than in SC alone. Conclusion: The fabricating antioxidant emulsions using heat-treated SC-TA are a good guarantee for the physical and oxidative stability of food formulations due to TA's intrinsic antioxidant properties and the protective role of SC-TA colloidal particles against coalescence.

Background: Dry powder inhalers (DPIs) are dosage forms that are used via the pulmonary route. Their formulations include two major parts; drug substance and carrier. For many years, DPIs have been made with lactose, a particularly popular carrier. Leucine has drawn more attention in recent years when it comes to DPI formulations made using the spray drying technique. Leucine was utilized in conjunction with carriers like lactose to enhance physicochemical and aerosolization properties. Method: In this investigation, when lactose and leucine were co-spray dried, the color of powders around the cyclone separators of the spray dryer turned brown while the produced powder in the collector was white. Both the white powder inside the collector and the brown powder around the cyclone separators were investigated by differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), and liquid chromatography with tandem mass spectrometry (LC-MS-MS) to determine the identity of the degraded chemicals and to look for any potential interactions. Results: A new peak at 177 ºC in DSC analysis is a sign of interaction. Also, FT-IR analysis shows the new peak at 1627 cm-1 which is related to the carbonyl group. According to SEM and XRD analysis co spray dried leucine-lactose is amorphous. Obtained data from LC-MS analysis indicates the adduct compound of leucine-lactose that resulted from the Maillard reaction was detected in both white and brown powder. Also, the reaction proceeded to form n-formyl compound. Conclusion: There is a possibility of lactose and leucine incompatibility during DPIs manufacturing, especially in elevated temperature and humidity.

Abstract Nanoparticle-based composites have the potential to meet requirements for radiosensitization in both therapeutic and diagnostic applications. The radiosensitizing properties of nanoparticles could be reliant on the nature of their coating layer. Any gains in reduced toxicity and aggregation or improved delivery to tumor cells for coated nanoparticles must be weighed against the loss of dose enhancement. The radiosensitization potential of coated NPs is confirmed by numerous studies but in most of them, the coating layer is mostly applied to reduce toxicity of the NPs and for stability and biocompatibility aims. While the direct effects of the coating layer in radiosensitization—were ignored and not considered. This review provides an overview of double-edged impact of nanoparticle coating on the radiosensitization potential of nanostructures and discusses the challenges in choosing appropriate coating material in the aim of achieving improved radioenhancement. Coating layer could affect the radiosensitization processes and thereby the biological outcomes of nanoparticle-based radiation therapy. The physicochemical properties of the coating layer can be altered by the type of the coating material and its thickness. Under low-energy photon irradiation, the coating layer could act as a shield for nanoparticles capable of absorb produced low-energy electrons which are important levers for local and nanoscopic dose enhancement. Also, it seems that the coating layer could mostly affect the chemical process of ROS production rather than the physicochemical process. Based on the reviewed literature, for the irradiated coated nanoparticles, the cell survival and viability of cancer cells are decreased more than normal cells. Also, cell cycle arrest, inhibition of cell proliferation, DNA damage, cell death and apoptosis were shown to be affected by coated metallic nanoparticles under irradiation.

Rice is one of the plants proven to possess antioxidant, anti-inflammatory, anti-proliferative, and whitening properties, making it one of the most beneficial plants in this regard. This study aimed to introduce a novel natural cosmetic and pharmaceutical product based on rice callus as a source of active ingredients that can inhibit skin melanoma cell (B16F10) proliferation and brighten the skin. The 2,4-D hormone at concentrations of 1 µg/mL and 1.5 µg/mL was used to induce rice callus formation. Rice callus extracts were then prepared using aqueous and ethanolic solvents, with a concentration of 1 mg/mL used for characterization tests. To determine the optimal hormone concentration, the phenols/flavonoids, antioxidant activity, proteins, and carbohydrates in the extracts were measured. The optimal concentration of the hormone was found to be 1 µg/mL. Finally, the anti-melanocyte and skin-whitening activity of the extracts was assessed through measurements of their cytotoxicity and inhibition of melanin synthesis-related enzymes. Cellular cytotoxicity measurements revealed that the ethanolic extract induced more cytotoxicity than the aqueous extract, with IC50 values of 566.3 µg/mL for the ethanolic extract and 1327 µg/mL for the aqueous extract. Skin-whitening-related tests demonstrated that the extracts were 1.7 times more effective than arbutin in inhibiting factors that cause hyperpigmentation. The aqueous extract achieved 85% inhibition of melanin biosynthesis at a concentration of 3200 µg/mL, compared to 68% for the ethanolic extract and 50% for arbutin. Based on these findings, rice callus extract can be introduced as a new, effective substance for skin-lightening and anti-melanocyte products in cosmeceutical and pharmaceutical formulations.

Purpose: Pennyroyal is a species of the Lamiaceae family with potent anti-cancer and antioxidant properties. Combining this antioxidant with chemotherapeutic agents enhances the effectiveness of these agents by inducing more apoptosis in cancerous cells. Methods: Here, methotrexate (MTX) combined with pennyroyal oil based on PEGylated nanostructured lipid carriers (NLCs) was assessed. These nanoparticles were physiochemically characterized, and their anti-cancer effects and targeting efficiency were investigated on the folate receptor-positive human breast cancer cell line (MCF-7) and negative human alveolar basal epithelial cells (A549). Results: Results showed a mean size of 97.4±12.1 nm for non-targeted PEGylated NLCs and 220.4±11.4 nm for targeted PEGylated NLCs, with an almost small size distribution assessed by TEM imaging. Furthermore, in vitro molecular anti-cancer activity investigations showed that pennyroyal-NLCs and pennyroyal-NLCs/MTX activate the apoptosis and autophagy pathway by changing their related mRNA expression levels. Furthermore, in vitro cellular studies showed that these changes in the level of gene expression could lead to a rise in apoptosis rate from 15.6±8.1 to 25.0±3.2 (P

Abstract Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates’ pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm−1 and 1650 cm−1, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics. Graphical Abstract

Curcumin has shown beneficial effects on pulmonary diseases with chronic inflammation or abnormal inflammatory responses, including chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. Clinical applications of curcumin are limited due to its chemical instability in solution, low water solubility, poor oral bioavailability, and intestinal and liver first-pass metabolism. Pulmonary delivery of curcumin can address these challenges and provide a high concentration in lung tissues. The purpose of the current work was to prepare a novel inhalable dry powder of curcumin nanocrystals without added excipients using electrospray drying (ED) with improved dissolution and aerosolization properties. ED of curcumin was performed at 2 and 4% w/v concentrations in acetone. Physicochemical properties of the formulated powders were evaluated by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), density and powder flow measurements, and in vitro dissolution. The in vitro deposition studies were conducted using next-generation impactor (NGI) and aerosol performance and aerodynamic particle size parameters were calculated for prepared formulations. ED could produce agglomerates of nanocrystals with a size of about 500 nm at an acceptable yield of about 50%. PXRD and FTIR data revealed that prepared nanocrystals were in a stable crystalline state. The bulk and tapped density of prepared agglomerates were in the range appropriate for pulmonary delivery. Formed nanocrystals could significantly improve the dissolution rate of water-insoluble curcumin. The optimized formulation exhibited acceptable recovered dose percentage, high emitted dose percentage, optimum mean mass median aerodynamic diameter, small geometric standard deviation, and high fine-particle fraction that favors delivery of curcumin to the deep lung regions. The ED proved to be an efficient technique to prepare curcumin nanocrystals for pulmonary delivery in a single step, at a mild condition, and with no surfactant.

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body’s antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P

Introduction: The present study was done to assess the effect of molecularly-targeted core/shell of iron oxide/gold nanoparticles (Fe3O4@AuNPs) on tumor radiosensitization of SKBr-3 breast cancer cells. Methods: Human epidermal growth factor receptor-2 (HER-2)-targeted Fe3O4@AuNPs were synthesized by conjugating trastuzumab (TZ, Herceptin) to PEGylated (PEG)-Fe3O4@AuNPs (41.5 nm). First, the Fe3O4@Au core-shell NPs were decorated with PEG-SH to synthesize PEG-Fe3O4@AuNPs. Then, the TZ was reacted to OPSS-PEG-SVA to conjugate with the PEG-Fe3O4@AuNPs. As a result, structure, size and morphology of the developed NPs were assessed using Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy. The SKBr-3 cells were treated with different concentrations of TZ, Fe3O4@Au, and TZ-PEG-Fe3O4@AuNPs for irradiation at doses of 2, 4, and 8 Gy (from X-ray energy of 6 and 18 MV). Cytotoxicity was assessed by MTT assay, BrdU assay, and flow cytometry. Results: Results showed that the targeted TZ-PEG-Fe3O4@AuNPs significantly improved cell uptake. The cytotoxic effects of all the studied groups were increased in a higher concentration, radiation dose and energy-dependent manner. A combination of TZ, Fe3O4@Au, and TZ-PEG-Fe3O4@AuNPs with radiation reduced cell viability by 1.35 (P=0.021), 1.95 (P=0.024), and 1.15 (P=0.013) in comparison with 8 Gy dose of 18 MV radiation alone, respectively. These amounts were obtained as 1.27, 1.58, and 1.10 for 8 Gy dose of 6 MV irradiation, respectively. Conclusion: Radiosensitization of breast cancer to mega-voltage radiation therapy with TZ-PEG-Fe3O4@AuNPs was successfully obtained through an optimized therapeutic approach for molecular targeting of HER-2.

Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC50 value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.

Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.

In the pharmaceutical industry, the microbiological quality of water is vital. This research investigated how combining peracetic acid (0.1% V/V) and UV light (>150 mJ/cm2) as wide-spectrum disinfectants affect microbial and endotoxin levels in a pharmaceutical water system. Water samples were taken aseptically from 12 points across the system. The pour plate technique and membrane filtration were used for microbial counts. The presence of endotoxin in distilled water samples was investigated by the Limulus amebocyte lysate (LAL) test gel-clot method. After peracetic acid–UV combination treatment, microbial counts of samples significantly decreased (P < 0.05) compared with UV treatment alone, and they were lower than the action limits specified by the European Pharmacopeia (100 CFU/ml for purified water and 10 CFU/100 ml for water for injection). In addition, water samples were mainly LAL-negative (10 negative weekly reports out of 12 total reports). It is concluded that disinfection of all stages of the water system with peracetic acid–UV combination remarkably improved the microbial quality of the water system. Therefore, rotation between more than one disinfectant policy and periodic disinfection of the water system by peracetic acid–UV combination is recommended to minimize contamination of the water system and pharmaceutical products as well as bacterial infections in product consumers. HIGHLIGHTS PAA–UV combination treatment for disinfection of water system of a pharmaceutical plant.; Six-month evaluations of the microbial quality (microbial count and endotoxin level of purified water and water for injection).; Individual control charts (I-chart) using microbial count data obtained 3 months with UV treatment alone and 3 months with a combination of PAA–UV treatment.;

Abstract Background and Aims SARS‐CoV‐2, as a new pandemic disease, affected the world. Short‐chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids are the main metabolites of human gut microbiota. The positive effects of SCFAs have been shown in infections caused by respiratory syncytial virus, adenovirus, influenza, and rhinovirus. Therefore, this study aimed to evaluate the concentration of SCFAs in patients with SARS‐CoV‐2 compared with the healthy group. Methods This research was designed based on a case and control study. Twenty healthy individuals as the control group and 20 persons admitted to the hospital with a positive test of coronavirus disease (COVID‐19) real‐time polymerase chain reaction were included in the study as the patient group from September 2021 to October 2021, in Tabriz, Iran. Stool specimens were collected from volunteers, and analysis of SCFAs was carried out by a high‐performance liquid chromatography system. Results The amount of acetic acid in the healthy group was 67.88 ± 23.09 μmol/g, while in the group of patients with COVID‐19 was 37.04 ± 13.29 μmol/g. Therefore, the concentration of acetic acid in the patient group was significantly (p 0.05). Conclusion This study showed that the concentration of acetic acid as the metabolite caused by gut microbiota is significantly disturbed in patients with COVID‐19. Therefore, therapeutic interventions based on gut microbiota metabolites in future research may be effective against COVID‐19.

Sepsis is a complex clinical disorder with heterogeneous etiological factors. Given its high mortality rate, it is considered a global health issue. Recently, the link between gut microbiota and their metabolites, especially short-chain fatty acids, in the pathophysiology of sepsis has been reported. However, there are few findings to confirm this relationship. This study aimed to evaluate some key gut microbiota members, pathogenic bacteria, and short-chain fatty acids in non-ICU patients with sepsis caused by bacteremia compared to a control group. In this case-control study, 45 stool samples from patients with sepsis and 15 healthy persons were collected from October 2021 to August 2022 in Tabriz, Iran. The position of some gut microbiota members and the main short-chain fatty acids concentration were assessed in the two groups by the Q-PCR and the high-performance liquid chromatography system. Faecalibacterium prausnitzii and Bifidobacterium sp. As bacterial with protective features in non-ICU patients with sepsis decreased significantly. Moreover, the concentrations of acetic acid and propionic acid significantly decreased in this group compared to the healthy volunteers. In contrast, the pathogenic bacteria members such as Enterobacteriaceae and Bacteroides sp. Increased significantly in the patients compared to the healthy individuals. The concentration of butyric acid decreased in the patients, but this change was not significant in the two groups. Protective and immune functions of F. prausnitzii and Bifidobacterium sp., as well as acetate and propionate, are evident. In this investigation, this profile was significantly reduced in non-ICU patients with sepsis compared to the control group.

Keypoints Zinc oxide (ZnO) and magnesium oxide (MgO) nanoparticles have themselves the intrinsic analgesic properties. The emergence of theranostic nanomedicine provides an ideal method for accurate pain management. Nanoneedles are new opportunities in the pain management. Many nanoliposomal analgesic formulations have been industrialized and are currently on the market.

Introduction: The use of pulmonary drug delivery as a non-invasive drug delivery system for the systemic treatment of diseases as well as the topical treatment of respiratory diseases is increasing. Among the various inhaled formulations, inhaled dry powders show advantages over the other forms of inhaled medicines due to high stability, bioavailability and ease of use. The effect of particle properties on the rate of drug delivery to the lungs in inhaled dry powders has been investigated in previous papers. Conclusion: Since the physicochemical properties of particles of dry powder inhalation formulations such as particle size, surface and particle shape, as well as the electrical charge of the particles play a decisive role in drug pharmacokinetics, in the present review article we intended to discuss the effect of these parameters of inhaled dry powder formulations on bioavailability, dissolution rate of drug particles and the rate of drug clearance from the body.

Purpose: Pulmonary tuberculosis (TB) is a worldwide life-threatening infection. Therecommended anti-TB regimen contains oral administration of classical first-line drugs suchas rifampin for 6-24 months which often leads to low patient compliance due to high adverseeffects; therefore, lung localized pulmonary delivery of anti-TB agents may be a suitablealternative. Proliposomes free-flowing powders are well-known carriers for lung delivery sincethey can form liposomes by hydration. Liposomes are safe and useful carriers for lung deliverydue to their phospholipid structure.Methods: Porous lactose and mannitol as proliposome carriers were prepared by spray dryingtechnique using sucrose and citric acid as templating agents. Design Expert® software wasused to develop forty formulations based on the porous and non-porous carriers, which werecharacterized with respect to their weight yield, density, and flowability. Rifampin-loadedhydrated liposomes were produced and evaluated for size, morphology, loading capacityand encapsulation efficiency. The optimized proliposomes in vitro release and aerosolizationproperties were evaluated. Solid-state analysis was confirmed by differential scanningcalorimetry (DSC).Results: Porous lactose surface area was 80 folds higher than non-porous one, respectively.Optimized porous-based proliposome indicated the acceptable aerosolization properties,including mass median aerodynamic diameter (MMAD) of 6.21 ± 0.36 μm and fine particlefraction (FPF) of 9.17 ± 0.18% with a fast rifampin release (80%) within one hour. DSC resultsproved that there was no change in the solid-state of rifampin during the production process.Conclusion: Hence, it seems; rifampin loaded inhalable proliposomes may be a suitable systemfor delivering liposomal rifampin into the lungs.

Abstract Purpose The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods Mono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results Well‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention. Conclusions S‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.

Upregulation of cyclooxygenase (COX-2) plays an important role in lung cancer pathogenesis. Celecoxib (CLX), a selective COX-2 inhibitor, may have beneficial effects in COVID-19-induced inflammatory storms. The current study aimed to develop carrier-free inhalable CLX microparticles by electrospraying as a dry powder formulation for inhalation (DPI). CLX microparticles were prepared through an electrospraying method using a suitable solvent mixture at two different drug concentrations. The obtained powders were characterized in terms of their morphology, solid state, dissolution behavior, and aerosolization performance. Electrosprayed particles obtained from the ethanol–acetone solvent mixture with a drug concentration of 3 % w/v exhibited the best in vitro aerosolization properties. The value of the fine particle fraction obtained for the engineered drug particles was 12-fold higher than that of the untreated CLX. When the concentration of CLX was increased, a remarkable reduction in FPF was obtained. The smallest median mass aerodynamic diameter was obtained from the electrosprayed CLX at a 3% concentration (2.82 µm) compared to 5% (3.25 µm) and untreated CLX (4.18 µm). DSC and FTIR experiments showed no change in drug crystallinity or structure of the prepared powders during the electrospraying process. The findings of this study suggest that electrospraying has potential applications in the preparation of DPI formulations.

Purpose: Hydrophilic drugs are extensively applied in clinical applications. Inadequate dermal penetration of these drugs is a great challenge. Incorporation of drugs into nano-carrier systems overcomes lower penetration drawbacks. Invasomes are novel nano-carrier systems which enhance transdermal penetration by using terpene and ethanol in their structures. buprenorphine and bupivacaine hydrochlorides are two potent analgesic drugs that are loaded simultaneously in the nano-invasome structure as opioid and non-opioid drugs. Methods: The full factorial experimental design was used for planning and estimating optimum formulations of invasome systems. Three influential factors like terpene type, terpene concentration and preparation method were comprehensively analyzed for achieving high encapsulation efficiency (EE) and optimum size. Results: The mean sizes of designed invasomes were in the range of 0.39-5.86 µm and high values of EE and loading capacity (LC) were reported as 98.77 and 19.75 for buprenorphine-loaded invasome, respectively. Zeta potential measurements confirmed that the obtained high value of EE might be as a result of reversible ionic interactions between positively charged drugs and negatively charged phospholipidic part of invasome structure. Another characterization of the prepared formulations was carried out by Fourier transform infrared (FTIR), X-ray diffraction (XRD) and dynamic light scattering (DLS) technique. Conclusion: The satisfactory obtained results of formulations encourage researchers to get optimum topical analgesic formulations with potent and rapid onset time properties required in invasive cutaneous procedures.

Abstract Apoptosis and antioxidant mechanisms are pathways for the treatment of endometriosis (Endo). Rutin (Rtn) is an antioxidant flavonol that induces apoptosis. This study, for first time, was conducted to evaluate the effects of rutin on Endo through apoptosis and antioxidant mechanisms. The experimental Endo was induced in 24 rats and then the animals were subdivided into Endo-sole, 3000 and 6000 µg/kg rutin (Rtn-3000 and Rtn-6000) and vitamin C groups. After 4 weeks, the expression of Bcl2, Bax, anti Pro Caspase-9, cleaved Caspase-9, pro PARP, pro Cleaved PARP, Pro PARP, pro mTOR and mTOR were assessed by western blotting technique. The protein concentrations of malondialdehyde (MDA), total antioxidant capacity, and super oxide dismutase and gutathione peroxidase were also evaluated. TUNEL staining was also used for the detection of apoptosis. Caspase-9 and concentration of antioxidants were higher in the treated groups compared to Endo-sole group (P

The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2 and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (

Abstract Background The expansion and metastasis of colorectal cancers are closely associated with the dynamic growth of cancer stem cells (CSCs). This study aimed to explore the possible effect of LXR (a regulator of glycolysis and lipid hemostasis) in the tumorgenicity of human colorectal CD133 cells. Methods Human HT-29 CD133+ cells were enriched by MACS and incubated with LXR agonist (T0901317) and antagonist (SR9243) for 72 h. Cell survival was evaluated using MTT assay and flow cytometric analysis of Annexin-V. The proliferation rate was measured by monitoring Ki-67 positive cells using IF imaging. The modulation of LXR was studied by monitoring the activity of all factors related to ABC transporters using real-time PCR assay and western blotting. Protein levels of metabolic enzymes such as PFKFB3, GSK3β, FASN, and SCD were also investigated upon treatment of CSCs with LXR modulators. The migration of CSCs was monitored after being exposed to LXR agonist using scratch and Transwell insert assays. The efflux capacity was measured using hypo-osmotic conditions. The intracellular content of reactive oxygen species was studied by DCFH-DA staining. Results Data showed incubation of CSCs with T0901317 and SR9243 reduced the viability of CD133 cells in a dose-dependent manner compared to the control group. The activation of LXR up-regulated the expression and protein levels of ABC transporters (ABCA1, ABCG5, and ABCG8) compared to the non-treated cells (p

In recent years, high atomic number nanoparticles (NPs) have emerged as promising radio-enhancer agents for cancer radiation therapy due to their unique properties. Multi-disciplinary studies have demonstrated the potential of NPs-based radio-sensitizers to improve cancer therapy and tumor control at cellular and molecular levels. However, studies have shown that the dose enhancement effect of the NPs depends on the beam energy, NPs type, NPs size, NPs concentration, cell lines, and NPs delivery system. It has been believed that radiation dose enhancement of NPs is due to the three main mechanisms, but the results of some simulation studies failed to comply well with the experimental findings. Thus, this study aimed to quantitatively evaluate the physical, chemical, and biological factors of the NPs. An organized search of PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed. In total, 77 articles were thoroughly reviewed and analyzed. The studies investigated 44 different cell lines through 70 in-vitro and 4 in-vivo studies. A total of 32 different types of single or core-shell NPs in different sizes and concentrations have been used in the studies.

Oxidative stress could be prevented by antioxidant-loaded nanoparticles. The purpose of this study was to assess the effects of 10 (A10), 20 (A20), 30 (A30), 40 (A40), and 50 (A50) μM alpha-lipoic acid and alpha-lipoic acid nanostructured lipid carriers (ALN) at 10 (ALN10), 20 (ALN20), 30 (ALN30), 40 (ALN40), and 50 (ALN50) μM on post-thawed sperm quality, fertility, and apoptosis-related genes of rooster sperm. The extender supplemented with ALN30 led to higher total and progressive motility, straight-line velocity, and linearity in comparison to the control group. The ALN30 resulted in higher percentage of mitochondria activity and glutathione peroxidase level compared with control (P < 0.05). The extender supplemented with ALN30 led to lower percentage of apoptotic sperm, when compared with the control. CASPASE 3 expression in ALN30 was lower (P

ABSTRACT: Antioxidant nanoparticles include the potential for improving sperm cryopreservation. The aim of performing this study was to evaluate the effects of gamma-oryzanol (GO) at 0 (C) (control group), 20 (GO20), 40 (GO40), 60 (GO60), 80 (GO80), and 100 (GO100) µM and gamma-oryzanol nanoparticles (GON) at 0 (CN), 20 (GON20), 40 (GON40), 60 (GO60), 80 (GON80), and 100 (GON100) µM on post-thawed sperm quality and fertility of rooster sperm. Sperm motility, plasma membrane integrity, total abnormality, mitochondrial activity (Rhodamine 123), apoptotic features (Annexin V/Propidium iodide), reactive oxygen species (ROS) production, ATP content and the fertility and hatchability were evaluated after thawing. Total motility in GON60 and GON80 were significantly higher compared to control groups (C and CN). GON80 showed the greatest percentages of progressive motilities. When GO80, GON60, and GON80 were added to the cryopreservation medium, the plasma membrane functionality of the semen samples improved. The minimum abnormality of spermatozoa is observed in the group treated with GON80. The groups treated with GON60 and GON80 had greater (P < 0.05) mitochondrial activity. The level of sperm ROS after cryopreservation was significantly lower in GON60 and GON80 groups. Live sperm was significantly higher (P < 0.05) in GON60 and GON80 group compared to other groups. GON60 and GON80 groups also led to the lowest significant percentage of apoptosis-like change sperm. Greater fertility percentages were observed (P < 0.05) when sperm were stored in extenders treated with GON60 and GON80. GON80 resulted in significantly improved hatched eggs compared to C, GO60, GO180 and CN. In conclusion, supplementation of Lake extender with 60 and 80 µM gamma-oryzanol nanoparticles could be a proper process to improve freeze-thawing rooster sperm quality leading to better freeze/thaw characteristics.

Background: Previous studies have examined the effect of resveratrol as a potent antioxidant for free radicals in semen. While, the prepared spermatozoa are more affected by ROS factors due to centrifugation and incubation. Objective: To evaluate the RSV's effects on the prepared sperm parameters and chromatin quality in both normozoospermic and asthenozoospermic cases before and after freezing. Materials and Methods: The sample of 10 normozoospermic and asthenozoospermic men was prepared through the swim-up method. The groups were then divided into two samples of control and experimental (exposure to 30 µmol/l of RSV) to evaluate and compare the sperm parameters and chromatin quality before and after freezing. Results: The motility and viability of spermatozoa were seen to be significantly different before and after freezing separately in the control and treatment samples of the groups (p ≤ 0.001 and p = 0.001, respectively). However, the stated difference between the control and treatment samples of normozoospermic and asthenozoospermic patients were not significant (p > 0.05). In addition, the sperm morphology and chromatin quality were not significantly different between the two samples of each group; nonetheless, chromatin quality of the treated sample was better than that of the control before and after freezing. Conclusion: Despite the protective effects of RSV on the semen samples, RSV cannot affect significantly the prepared sperms parameters and chromatin quality in normozoospermic and asthenozoospermic patients.Key words: Resveratrol, Chromatin, Motility, Spermatozoa, Freeze.

Purpose: The aim of this study was to evaluate the influence of the geometric shape on the dissolution rate of the domperidone, a drug model for immediate release dosage form. In this regard, a lack of sufficient information about the effective dissolution rate of the drugs regarding their shapes has made this issue an interesting subject for researchers. Methods: For this purpose, three tablet shapes, namely flat and biconvex both in a round and oblong shapes, with different four sizes were modelled for the preparation of domperidone tablet. In vitro dissolution test was accomplished using a USP dissolution apparatus II. The drug dissolution rate was assessed by calculating various dissolution parameters; e.g., dissolution efficiency (DE), mean dissolution rate (MDR), mean dissolution time (MDT), and difference and similarity factors (f1 and f2 ). Results: Regarding the disintegration time, the larger tablets showed a faster disintegration time. When the size of the tablets was smaller, the amount of released drug was significantly decreased. In addition, #9 tablets with a flat or biconvex geometry had obvious effects on the DE values. Generally, biconvex tablets had higher DE percentage than the flat tablets. Conclusion: Noticeable differences in dissolution parameters by considering the different geometric shapes play an important role in the drug release kinetics which makes a significant effect on quick onset of action in oral administration.

Background: This study is an attempt to investigate the effect of nano-liposome containing voriconazole on voriconazole-resistant A. flavus strains on the one hand, and to consider the expression of cyp51A and MDR1genes, regarded as important genes involved in the development of resistance to triazoles before and after voriconazole and voriconazole-loaded nano-liposomes exert their effects, on the other hand.Methods: Strains of A. flavus isolated from patients were investigated and their susceptibility to voriconazole was determined. Next, having applied a slight modification to the thin film hydration-sonication technique, the liposomal formulation of voriconazole was produced. After that, the voriconazole-loaded nano-liposome was subjected to in-vitro antifungal susceptibility testing to obtain minimum inhibitory concentration against fungal isolates. Cyp51A and MDR1 mRNA levels were amplified by qRT-PCR instrument.Results: The effect of nano-liposome containing voriconazole on the reduction of MIC in A. flavus isolates were considered to be significant. After using MIC50 concentration of VCZ, the cyp51A gene expression in voriconazole-susceptible A. flavus strains and voriconazole-resistant strains 10folds and 7folds depicted a downregulation, respectively, which was more pronounced in the expression of a liposomal formulation of VCZ (13folds and 15folds respectively). Identically, the same procedure was applied to MDR1, even though it induced 1, 2, 3, 4-fold reductions.Conclusion: Considering the benefits of liposome-containing voriconazole formulation, such as the reduction of the side effects of the pure drug as well as minimizing the drug's toxicity coupled with the enhanced drug bioavailability and stability, the formulation can be used in drug-sensitive and drug-resistant species.

Purpose: The increase of bacterial resistance to common antibacterial agents is one of the major problems of health care systems and hospital infection control programs. In this study, antimicrobial activity of titanium dioxide (TiO2 ) and zinc oxide (ZnO) nanoparticles (NPs) was investigated against E. coli, Salmonella enteritidis, Listeria monocytogenes, and Staphylococcus aureus pathogenic bacteria by determining sensitivity coefficient and kinetics of bacterial death. Methods: Antimicrobial tests were performed with ~106 CFU/mL of each bacterium at baseline. At first, minimum inhibitory concentration (MIC) was concluded by the dilution method and then, death kinetic and susceptibility coefficient of NPs suspensions was determined at 0 to 360 min. treatment time. Results: The results of this study revealed that, the highest susceptibility was observed for L. monocytogenes (Z=0.025 mL/μg) to TiO2 NPs, whereas the lowest susceptibility was obtained in the reaction of ZnO NPs with S. enteritidis (Z=0.0033 mL/μg). The process of bacterial death in NPs suspension was assumed to follow first-degree kinetic and the survival ratio of bacteria decreased by the increase in treatment time. An increase in the concentration of NPs was seen to enhance the bactericidal action. Conclusion: Results showed that L. monocytogenes had higher sensitivity compared to S. enteritidis. The results of this study also demonstrated that TiO2 NPs have a strong antimicrobial effect in comparison with ZnO NPs and it could be employed to aid the control of pathogenic bacteria.

Abstract Cinnamon essential oil is known to have antioxidant and antibacterial properties, which may accelerate, wound healing. This study was conducted to evaluate the effects of an ointment prepared from Cinnamon verum essential oil (C verum) in infected wound model. An experimentally excisional infected wound model was induced in mice. Circular excisional wound model of 5 mm surface area was surgically created and inoculated with 107 CFU of each of two bacterial strains of Staphylococcus aureus and Pseudomonas aeruginosa. The animals were divided into three groups and topically treated with soft yellow paraffin (control) and ointments containing 2% and 4% C verum. The mRNA levels of insulin‐like growth factor I (IGF‐1), fibroblast growth factor‐2 (FGF‐2) and vascular endothelial growth factor (VEGF), epidermal keratin, fibroblasts, fibrocytes, immune cells, and vascular distribution as well as epithelialization ratio were investigated in order to evaluate the effects of C verum on wound healing. Tissue total antioxidant capacity and malondialdehyde levels (MDA) were also evaluated. Topical administration of C verum remarkably shortened the inflammatory phase, increased fibroblast distribution, collagen deposition, and accelerated the cellular proliferation, reepithelialization and keratin synthesis. The mRNA levels of IGF‐1, FGF‐2 and VEGF were remarkably higher in C verum‐treated groups (especially 2%) in comparison control group. Topical administration of C verum increased antioxidant power and reduced MDA content in comparison to control animals. C verum accelerates wound healing by upregulating the IGF‐1, FGF‐2, and VEGF expression and increasing cell proliferation, collagen synthesis, and reepithelialization ratio.

Abstract Background The larval stage of the tapeworm Echinococcus granulosus is the causative agent of hydatid disease in humans. This zoonotic parasitic infection remains a major health problem in certain areas of the world where is still endemic. In view of the ineffectiveness of some drug treatments, the surgical removal of cysts remains the preferred treatment option together with the administration of albendazole and mebendazole. However, severe side effects of these drugs have been reported which demands developing new scolicidal agents that confer suitable efficacy and fewer side effects during surgery. Methods To that purpose, in the present work we assessed the effectiveness of ivermectin (IVM), a macrocyclic lactone endectocide that has shown to be an effective nematocidal drug against other important parasitic infections. To overcome the limitations observed in some drug formulations and resistance, we used nano lipid carriers (NLCs) as a targeted and sustained drug delivery system for IVM. We evaluated the in vitro cestocidal and apoptotic effects of NLCs-loaded IVM versus IVM by quantifying the expression of caspase-3 mRNA. Results We found that after 60 and 120 min of administration, 800 μg/ml and 400 μg/ml NLCs-loaded IVM induced 100% mortality, respectively. On the other hand, the 800 μg/ml of IVM induced 100% mortality rate 150 min after administration. Additionally, we found that NLCs-loaded IVM induced higher mRNA caspase-3 expression suggesting a more potent apoptotic effect on the parasite. Conclusions These data suggest that NLCs-loaded IVM may be a promising alternative to current treatments although in vivo studies are needed.

Betanin is a bioactive compound with a high antioxidant activity and therapeutic potential. However, incomplete oral absorption and low stability of betanin limit its application. To surmount these limitations, betanin was encapsulated with nanoliposomes, nanoparticles exhibiting suitable physicochemical properties. Additionally, betanin-loaded nanoliposomes revealed a relatively good sustained release profile in the simulated gastric and intestinal fluids. In vitro digestion stability of betanin and its antioxidant activity were significantly improved by liposomal encapsulation. These nanocarriers were assessed in vivo for their therapeutic potency in streptozotocin induced rats. The results showed that the administration of betanin-loaded nanoliposomes was significantly more effective than free betanin in positively regulate hyperglycemia, hyperlipidemia and oxidative stress. Moreover, the histopathological analysis showed that the tissue damage in kidney, liver and pancreas was reduced in the betanin-loaded nanoliposomes treated diabetic rats. In conclusion nanoliposomes are suitable nanocarriers for improving the stability and therapeutic potential of betanin.

Purpose: Hydrophobic nutraceuticals are suffering from water solubility and physicochemical stabilities once administered to the body or food matrixes. The present study depicts the successful formulation of a zein-carboxymethyl cellulose (CMC) complex to stabilize a water in oil (W/O) emulsion to protect them from environmental and gastrointestinal conditions. The formulated water in oil in water (W/O/W) system was used for nanoencapsulating of hydrophobic nutraceutical, rutin, via protein-polysaccharide complexes. Methods: Zein nano particles smaller than 100 nm were produced using poly ethylene glycol (PEG 400) and Tween 80, which eliminates the use of ethanolic solutions in preparation of zein nanoparticles (ZN). CMC was then added to the ZN under magnetic stirrer to provide zein-CMC complex. A concentration of 20% CMC showed the smallest particle size (

Purpose: In this study, we aimed to prepare an extended drug delivery formulation ofclarithromycin (CAM) based on a semi-interpenetrating polymer network (semi-IPN) hydrogel.Methods: Synthesis of semi-IPN hydrogel nanocomposite made of chitosan (CS), acrylicacid (AA), acrylamide (AAm), polyvinylpyrrolidone (PVP), and montmorillonite (MMT) wasperformed by free radical graft copolymerization method. Swelling kinetic studies were done inacidic buffer solutions of hydrochloric acid (pH = 1.2), acetate (pH = 4), and also distilled water.Also, the effects of MMT on the swelling kinetic, thermal stability, and mechanical strengthof the hydrogels were evaluated. Moreover, in vitro release behavior of CAM and its releasekinetics from hydrogels were studied in a hydrochloric acid buffer solution.Results: Fourier transform infrared spectroscopy (FTIR) results revealed that synthesis of semi-IPN superabsorbent nanocomposite and CAM incorporation into hydrogel was performed,successfully. Introducing MMT into hydrogel network not only improved its thermal stabilitybut also increased mechanical strength of the final hydrogel product. Also, in comparisonwith neat hydrogel (1270 g/g), hydrogel nanocomposite containing 13 wt% MMT exhibitedgreater equilibrium swelling capacity (1568 g/g) with lower swelling rate. In vitro drug releaseexperiments showed that CS-g-poly(AA-co-AAm)/PVP/MMT/CAM formulation possesses asustained release character over extended period of time compared with CS-g-poly(AA-co-AAm)/PVP/CAM formulation.Conclusion: In the presence of MMT, the effective life time of drug is prolonged, demonstrating asustained release property. The reason is that interlinked porous channels within superabsorbentnanocomposite network hinder penetration of aqueous solutions into hydrogel and subsequentlycause a slower drug release.

Purpose: In the current study, we aimed to look into the macroscopic and microscopic dose enhancement effect of metallic nanoparticles in interstitial brachytherapy of gastric adenocarcinoma by Iodine-125 source using a nano-lattice model in MCNPX (2.7) and MCNP6.1 codes. Materials and methods: Based on a nano-lattice simulation model containing a radiation source and a tumor tissue with cellular compartments loaded with 7 mg/g spherical nanoparticles, the microscopic and macroscopic levels of energy deposition by the secondary electrons was estimated. Results: The results show that the values of macroscopic DEF are higher than microscopic DEF values and the macroscopic DEF values decrease by increasing the distance from the surface of brachytherapy source. Accordingly, it could be noted that gold nanoparticles have the highest radiosensitization effect among the other nanoparticles and the related DEF value is close to the resultant DEF values for bismuth nanoparticles. Moreover, the results revealed a remarkable discrepancy between the DEF and secondary electron spectra calculated by MCNPX (2.7) and MCNP6.1 codes, which could be justified by the difference in energy cut-off and electron transport algorithms of two codes. Conclusions: According to the both MCNPX (2.7) and MCNP6.1 outputs, it could be concluded that the presence of metallic nanoparticles in the tumor tissue of gastric adenocarcinoma increases the physical effectiveness of brachytherapy by I-125 source. This study aims to provide recommendations for future preclinical studies. Actually, the results presented herein give a physical view of radiosensitization potential of different metallic nanoparticles and could be considered in design of analytical and experimental radiosensitization studies in tumor regions using various radiotherapy modalities in the presence of heavy nanomaterials.

In the last few decades, various bioactive compound-delivery technologies have been emerged and nanoscale delivery devices have been developed. Nanostructured lipid carriers (NLCs) are delivery systems that reveal some advantages over conventional carriers such as increased loading capacity, encapsulation efficiency, solubility, storage stability, bioavailability, and half-life. Moreover, they provide controlled compound release and safety for food systems. In this review, aspects of NLCs, their components, production methods, bioactive compound incorporation, release, stability, and food applications are introduced.

It has been hypothesized that simvastatin could be used to treat pulmonary arterial hypertension (PAH). This study is intended to formulate a simvastatin nanoparticle dry powder inhalation (DPI) formulation. Simvastatin nanoparticles were prepared via an emulsification and homogenization-extrusion method, followed by spray drying of the colloidal suspension of simvastatin nanoparticles containing mannitol to get it into a respirable size. Particle size distribution, morphology, and crystallinity of the fabricated nanoparticles of the obtained microparticles for DPI formulation were assessed by dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction pattern (XRPD), respectively. Aerosolization performance of the DPI formulation was assessed by the Next Generation Impactor (NGI) equipped with an Aerolizer®. Simvastatin nanoparticles were around 100 nm with a very narrow size distribution (PDI = 0.105). The X-ray diffraction pattern revealed that the crystallinity of simvastatin was decreased by the spray drying procedure. Microscopic images displayed that gathered nanoparticles were in the suitable inhalable range and had the appropriate shape and surface properties for pulmonary delivery. Aerosolization assessment by the NGI indicated a suitable inhalation performance (fine particle fraction of 20%). In conclusion, the results confirmed that the spray drying technique for simvastatin can be optimized to obtain simvastatin aggregated nanoparticles without any coarse carrier to be used in DPI formulation for better deposition of the drug in the lungs for local treatment of PAH.

Purpose: To potentially enhance the bioavailability and extend the bioactivity effectiveness of Isoleucine-Proline-Proline (IPP, an antihypertensive bioactive peptide of dairy origin), a novel Lyotropic Liquid Crystalline Pharmacosomal Nanoparticle (LLCPNP) was synthesized, and its physicochemical and technological characteristics were studied. Methods: LLCPNPs precursors were developed using IPP and soy phosphatidylcholine via complex formation. Polarized light microscopy, small angle X-ray scattering, differential scanning calorimetry, dynamic light scattering and Fourier transform infrared spectroscopy were employed to characterize the physicochemical properties of the nanoparticles. The in-vitro release and its related mechanisms were also studied. Results: Fourier transform infrared spectroscopy confirmed the complexation between the components of LLCPNPs. Phase behavior evaluation by polarized light microscope showed the characteristic birefringent texture. These findings along with those of small angle X-ray scattering and differential scanning calorimetry proved the formation of lamellar LLCPNPs. These particles represented nanometric size (

Background: Respiratory fungal diseases therapy is still facing challenges as a result of increasing autoimmune disorders, cancers, and immunosuppressive medication usage. Fluconazole is a wide spectrum antifungal agent and is still used successfully in the treatment of opportunistic infections in combination with other antifungal agents. Since, the treatment of respiratory fungal diseases requires prolonged hospitalization; it may increase the chances of other opportunistic infections. Considering the reported drug resistance and adverse effects of systemic administration, it appears that localized pulmonary antifungal therapy may be a suitable alternative route. According to the reported suitable inhalation properties of spray dried powders; spray drying technique was used to prepare fluconazole powders. Methods: Different spray drying parameters such as inlet temperature, pump rate, aspiration%, solvent type, as well as fluconazole concentration were evaluated for powder production. The optimized formulations were characterized using scanning electron microscopy (SEM), x-ray diffraction (XRD), differential scanning calorimetry (DSC) and aerodynamic parameters. Results: All selected formulations showed a smooth surface with similar mass median aerodynamic diameter (MMAD) in a respiratory acceptable range. While optimized powder showed a lower geometric standard deviation (GSD) of 1.5 with higher fine particle fraction (FPF) of 26% and almost complete deposition recovery of 97%. Conclusion: Based on in vitro characterization results, it appears that spray drying is an appropriate and cost-effective technique for the production of inhalable fluconazole powder. It is characterized by a narrower size distribution and delivers a higher dose which may be more cost effective for mass production.

Emulsifiers are a large category of compounds considered as surface active agents or surfactants. An emulsifier acts by reducing the speed of chemical reactions, and enhancing its stability. Bioemulsifiers are known as surface active biomolecule materials, due to their unique features over chemical surfactants, such as non-toxicity, biodegradability, foaming, biocompatibility, efficiency at low concentrations, high selectivity in different pH, temperatures and salinities. Emulsifiers are found in various natural resources and are synthesized by Bacteria, Fungi and Yeast. Bioemulsifier’s molecular weight is higher than that of biosurfactants. Emulsion’s function is closely related to their chemical structure. Therefore, the aim of this paper was to study the various bioemulsifiers derived from microorganisms used in the drug and food industry. In this manuscript, we studied organisms with biosurfactant producing abilities. These inexpensive substrates could be used in environmental remediation and in the petroleum industry.

Background: The formation of electrostatic complexes between two types of biopolymers, sodium Caseinate (a derivative from most abundant milk protein) and Pectin (a natural hetro polysaccharide), was studied as a function of biopolymers concentrations and pH of solutions (3.9- 4.3). Method: The size and morphology of the resulted complexes were investigated by using of laser light scattering and transmission electron microscopy, respectively. Response surface methodology (A three-factor, three levels Box-Behnken design) was used for the optimization procedure with pH, pectin and sodium Caseinate concentrations as independent variables. Particle size and polydispersity index of nanocomplexes were considered as dependent variables. Results: Negatively charged nanocomplexes were produced below the isoelectric point of protein (5.4), at pH 4.1 with a suitable colloidal stability and average particle size of about 100 nm. It was found that the particle size of nanocomplexes could be controlled by changing in variables. Conclusion: In conclusion response surface methodology are simple, rapid and beneficial approach for preparation, optimization and investigation of the effect of independent variables on the properties of products.