Enhancing the Topical Antibacterial Activity of Fusidic Acid via Embedding into Cinnamon Oil Nano-Lipid Carrier.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box-Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system.

Date Palm Extract (Phoenix dactylifera) Encapsulated into Palm Oil Nanolipid Carrier for Prospective Antibacterial Influence.

It is worthwhile to note that using natural products today has shown to be an effective strategy for attaining the therapeutic goal with the highest impact and the fewest drawbacks. In Saudi Arabia, date palm (Phoenix dactylifera) is considered the principal fruit owing to its abundance and incredible nutritional benefits in fighting various diseases. The main objective of the study is to exploit the natural products as well as the nanotechnology approach to obtain great benefits in managing disorders. The present investigation focused on using the powder form of date palm extract (DPE) of Khalas cultivar and incorporates it into a nanolipid formulation such as a nanostructured lipid carrier (NLC) prepared with palm oil. Using the quality by design (QbD) methodology, the most optimized formula was chosen based on the number of assigned parameters. For more appropriate topical application, the optimized DP-NLC was combined with a pre-formulated hydrogel base forming the DP-NLC-hydrogel. The developed DP-NLC-hydrogel was evaluated for various physical properties including pH, viscosity, spreadability, and extrudability. Additionally, the in vitro release of the formulation as well as its stability upon storage under two different conditions of room temperature and refrigerator were investigated. Eventually, different bacterial strains were utilized to test the antibacterial efficacy of the developed formulation. The optimized DP-NLC showed proper particle size (266.9 nm) and in vitro release 77.9%. The prepared DP-NLC-hydrogel showed acceptable physical properties for topical formulation, mainly, pH 6.05, viscosity 9410 cP, spreadability 57.6 mm, extrudability 84.5 (g/cm2), and in vitro release 42.4%. Following three months storage under two distinct conditions, the formula exhibited good stability. Finally, the antibacterial activity of the developed DP-NLC-hydrogel was evaluated and proved to be efficient against various bacterial strains.

A century of "Camel Research": a bibliometric analysis.

Introduction: Bibliometrics is a quantitative analytic strategy used to assess the unit of publications per each field of research. Bibliometric studies are commonly employed to examine the current research climate, potential developments, and development trends in certain domains. In this work, the major contributors to camel research throughout the past century are discussed, along with the funding sources, academic institutions, scientific disciplines, and countries that contributed to "Camel Research". Methods: The Web of Science (WOS) database was used to retrieve the publications based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) instructions. Results: There are 7,593 articles dedicated to camel research on the Web of Science (as of August 1st, 2022). Three stages were involved in the publication of a study on camels. At the beginning, from 1877 to 1965, there were fewer than ten new publications per year. The second stage comprised 100 publications per year (1968-2005). Since 2010, nearly 200 new papers have been published each year. King Saud and King Faisal universities contributed > (0.08) of the total publications. While more than 1,000 funding agents were retrieved, the Natural Science Foundation of China (NSFC) showed the greatest rate of funded projects (0.17). Camel research was included in 238 scientific disciplines. The top disciplines were Veterinary Sciences (0.39), Agriculture Dairy Animal Science (0.144), and Food Science Technology (0.087). Conclusion: There has been an increase in interest in camels in recent years, but the research trends in camel health and production need greater support.

Pharmacological Features of 18ß-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18ß-glycyrrhetinic acid (18ßGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18ßGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18ßGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18ßGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18ßGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18ßGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Tea Tree Oil Nanoemulsion-Based Hydrogel Vehicle for Enhancing Topical Delivery of Neomycin.

The present investigation aims to improve the antimicrobial influence of certain antibacterial drugs, namely, neomycin (NEO), exploiting the benefits of natural oils such as tea tree oil (TTO). Therefore, a distinctive nanolipid formulation, namely, a nanoemulsion (NE), was developed using a Central Composite Factorial Design (CCD) approach depending on the amount of TTO and tween 80 as surfactant. The optimized NEO-NE formula exhibiting minimum globular size and maximum in vitro release was selected. For efficient topical delivery, NEO-NE was incorporated into a pre-formulated hydrogel. The developed NEO-NE-hydrogel was characterized by its physical characteristics such as pH, viscosity, and spreadability. Next, it was tested for stability under different conditions for 3 months. Ultimately, an irritation test was conducted followed by an antibacterial examination. The preparation demonstrated acceptable properties to be successfully applied topically. It showed non-significant changes in stability in both conditions up to 3 months storage when compared to a fresh preparation. It exhibited no irritation when applied on hairless animal skin. Finally, TTO revealed a good inhibition for the bacterial growth that could improve the influence of NEO antibacterial activity, indicating the efficiency of NE containing NEO prepared with TTO to be a promising antibacterial nanocarrier.

Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.

Evaluating Antimicrobial Activity and Wound Healing Effect of Rod-Shaped Nanoparticles.

Presently, the nanotechnology approach has gained a great concern in the media of drug delivery. Gold nanoparticles (Au-NPs) specially having a non-spherical structure, such as gold nanorods (GNR), are attracting much interest as antibacterial agent and many other medical fields. The aim of the current investigation was to characterize Au-NPs and investigate their antimicrobial and wound healing efficacy in diabetic animals. MATERIAL AND METHODS: Au-NPs were characterized using a UV-Vis spectrophotometer, estimating their particle size, polydispersity (PDI), and assessing their morphological characters. Further, Au-NPs were estimated for their antibacterial and antifungal behavior. Ultimately, in vivo activity of Au-NPs was evaluated against excision wound healing in STZ-induced diabetic animals. RESULTS: Au-NPs were found to show maximum absorption at 520 nm. They exhibited a particle size of 82.57 nm with a PDI value of 0.323. Additionally, they exhibited good antimicrobial activity against different bacterial strains. Topical application of Au-NPs caused a significantly increased percentage of wound area reduction, lesser time needed for epithelialization, and augmented hydroxyproline, collagen, and hexosamine levels demonstrating enhanced healing processes. Furthermore, Au-NPs displayed a significant intensification in angiogenesis-related factors (HIF-1α, TGF-ß1, and VEGF), and antioxidant enzymes activities (CAT, SOD, GPx) as well as mitigated inflammatory mediators IL-6, IL-1ß, TNF-α, and NF-κB) and lipid peroxidation (MDA). CONCLUSION: Au-NPs exhibited proper particle size, and rod-shaped particles, with efficient antimicrobial behavior against different bacterial strains. Furthermore, Au-NPs demonstrated a promising wound healing activity in STZ-induced diabetic animals.

Shea Butter Potentiates the Anti-Bacterial Activity of Fusidic Acid Incorporated into Solid Lipid Nanoparticle.

Fusidic acid (FA) is an efficient anti-bacterial drug proven to be efficient against a wide range of bacteria. Nevertheless, the main restriction in its formulation is the limited solubility. To avoid such an obstacle, the drug is incorporated into the lipid core of the nanolipid formulation. Consequently, the present study was an attempt to formulate nanolipid preparation, mainly, solid lipid nanoparticle (SLN) integrating FA. FA-SLN was prepared using shea butter as a lipid phase owing to its reported anti-bacterial activity. Different FA-SLNs were fabricated using the central composite design (CCD) approach. The optimized formula was selected and integrated into a hydrogel base to be efficiently used topically. FA-SLN-hydrogel was evaluated for its character, morphology, in vitro release and stability. The formula was examined for irritation reaction and finally evaluated for its anti-bacterial performance. The optimized formula showed particle size 283.83 nm and entrapment 73.057%. The formulated FA-SLN-hydrogel displayed pH 6.2, viscosity 15,610 cP, spreadability 51.1 mm and in vitro release 64.6% following 180 min. FA-SLN-hydrogel showed good stability for three months at different conditions (room temperature and refrigerator). It exhibited no irritation reaction on the treated rats. Eventually, shea butter displayed a noteworthy effect against bacterial growth that improved the effect of FA. This would indicate prospective anti-bacterial activity of FA when combined with shea butter in SLN formulation as a promising nanocarrier.

Novel Formulation of Fusidic Acid Incorporated into a Myrrh-Oil-Based Nanoemulgel for the Enhancement of Skin Bacterial Infection Treatment.

Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box−Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.

Phenotypic characterization of NKT-like cells and evaluation of specifically related cytokines for the prediction of unexplained recurrent miscarriage.

PROBLEM: Immune system dysregulation is a major cause of unexplained recurrent miscarriage (URM). Women with URM need screening for their pregnancy microenvironment and immune regulators, to prevent spontaneous abortion. METHOD OF STUDY: In this study we evaluated NKT-like cell subsets in peripheral venous blood of women with URM using flow cytometry. The expression levels of specifically related Th1 cytokines (IFN-γ and IL-2), Th2 cytokine (IL-4), and Th17 cytokines (IL-17), were measured using enzyme-linked immunosorbent assay. RESULTS: The percentage of CD16+CD56+NKT-like (Double Positive NKT-like; DPNKT-like) cell subset, and the levels of IL-2 and IFN-γ were significantly elevated in blood of non-pregnant and pregnant patients with URM compared with the healthy control groups, and these parameters were significantly increased after pregnancy in the same patients with URM. Based on the prevalence of the candidate immunological factors in patients with URM, the prognostic significance of the NKT-like cell subsets, IFN-γ and IL-2 profiles were evaluated as potential predictors of URM. A cut-off point of 2.55% for DPNKT-like cell subset in the blood and cut-off values of 39.5 and 20.5 pg/ml for the levels of IFN-γ and IL-2, respectively could be used for the prediction of the risk of spontaneous abortion. To the best of our knowledge, this is the first study that described the prognostic significance of the aforementioned immunological parameters before and after pregnancy, and highlighted the correlation of NKT-like cells and the candidate Th1 cytokines with pregnancy loss in women with URM. CONCLUSIONS: DPNKT-like cells, IFN-γ and IL-2 patient profiles could be used as markers to predict the risk of miscarriage in patients with URM.

Molecular Detection of Fluoroquinolone Resistance among Multidrug-, Extensively Drug-, and Pan-Drug-Resistant Campylobacter Species in Egypt.

In recent times, resistant foodborne pathogens, especially of the Campylobacter species, have created several global crises. These crises have been compounded due to the evolution of multidrug-resistant (MDR) bacterial pathogens and the emergence of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Therefore, this study aimed to investigate the development of resistance and the existence of both XDR and PDR among Campylobacter isolates. Moreover, we explored the use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for the detection of fluoroquinolone (FQ)-resistant Campylobacter isolates. A total of 120 Campylobacter isolates were identified depending on both phenotypic and genotypic methods. Of note, cefoxitin and imipenem were the most effective drugs against the investigated Campylobacter isolates. Interestingly, the majority of our isolates (75%) were MDR. Unfortunately, both XDR and PDR isolates were detected in our study with prevalence rates of 20.8% and 4.2%, respectively. All FQ-resistant isolates with ciprofloxacin minimum inhibitory concentrations ≥4 µg/mL were confirmed by the genetic detection of gyrA chromosomal mutation via substitution of threonine at position 86 to isoleucine (Thr-86-to-Ile) using the PCR-RFLP technique. Herein, PCR-RFLP was a more practical and less expensive method used for the detection of FQ resistant isolates. In conclusion, we introduced a fast genetic method for the identification of FQ-resistant isolates to avoid treatment failure through the proper description of antimicrobials.

Pancreatin-Cetyl Pyridinium Chloride Digestion and Decontamination Method; A Novel, Sensitive, Cost-Effective Method for Culturing Mycobacterium tuberculosis.

The present study evaluated the performance of newly developed pancreatin-cetylpyridinium chloride (pancreatin-CPC) digestion and decontamination method (DDM) with N-acetyl L-Cysteine-sodium hydroxide (NALC-NaOH) DDM for isolation of Mycobacteria from clinically suspected pulmonary tuberculosis (PTB) patients. For the study, sputum samples (n = 613) obtained from clinically suspected PTB cases were subjected to direct microscopy, pretreatment with NALC-NaOH DDM (reference method), and pancreatin-CPC DDM followed by culture, and the data were analyzed. The direct microscopy illustrated diagnostic accuracies of 60.4% (sensitivity), 99.77% (specificity), 98.9% (positive predictive value) and 88.3% (negative predictive value), respectively (against culture) for the detection of Mycobacterial species. The pancreatin-CPC DDM showed competitive diagnostic accuracies (against NALC-NaOH DDM) of 99.32% (sensitivity), 94.07% (specificity), 85.05% (positive predictive value), and 99.76% (negative predictive value), respectively, for the isolation of Mycobacterial species. In conclusion, pancreatin-CPC DMM was a highly sensitive, technically simple, and cost-effective method, suggesting its competence to substitute the currently used NALC-NaOH DDM.

Geraniol isolated from lemon grass to mitigate doxorubicin-induced cardiotoxicity through Nrf2 and NF-κB signaling.

BACKGROUND: Geraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. RESULTS: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. CONCLUSION: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.

Biogenic and biocompatible silver nanoparticles for an apoptotic anti-ovarian activity and as polydopamine-functionalized antibiotic carrier for an augmented antibiofilm activity.

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.

Quality by Design for Development, Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery.

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.

Xylitol Inhibits Growth and Blocks Virulence in Serratia marcescens.

Serratia marcescens is an opportunistic nosocomial pathogen and causes wound and burn infections. It shows high resistance to antibiotics and its pathogenicity is mediated by an arsenal of virulence factors. Another therapeutic option to such infections is targeting quorum sensing (QS), which controls the expression of different S. marcescens virulence factors. Prevention of QS can deprive S. marcescens from its bacterial virulence without applying stress on the bacterial growth and facilitates the eradication of the bacteria by immunity. The objective of the current study is to explore the antimicrobial and antivirulence activities of xylitol against S. marcescens. Xylitol could inhibit the growth of S. marcescens. Sub-inhibitory concentrations of xylitol could inhibit biofilm formation, reduce prodigiosin production, and completely block protease activity. Moreover, xylitol decreased swimming motility, swarming motility and increased the sensitivity to hydrogen peroxide. The expression of rsmA, pigP, flhC, flhD fimA, fimC, shlA bsmB, and rssB genes that regulate virulence factor production was significantly downregulated by xylitol. In silico study showed that xylitol could bind with the SmaR receptor by hydrophobic interaction and hydrogen bonding, and interfere with the binding of the natural ligand with SmaR receptor. An in vivo mice survival test confirmed the ability of xylitol to protect mice against the virulence of S. marcescens. In conclusion, xylitol is a growth and virulence inhibitor in S. marcescens and can be employed for the treatment of S. marcescens wound and burn infections.

Enhancement of Curcumin Anti-Inflammatory Effect via Formulation into Myrrh Oil-Based Nanoemulgel.

BACKGROUND: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. METHODS: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. RESULTS: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). CONCLUSIONS: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

Repurposing of antidiabetics as Serratia marcescens virulence inhibitors.

BACKGROUND: Serratia marcescens becomes an apparent nosocomial pathogen and causes a variety of infections. S. marcescens possess various virulence factors that are regulated by intercellular communication system quorum sensing (QS). Targeting bacterial virulence is a proposed strategy to overcome bacterial resistance. Sitagliptin anti-QS activity has been demonstrated previously and we aimed in this study to investigate the effects of antidiabetic drugs vildagliptin and metformin compared to sitagliptin on S. marcescens pathogenesis. METHODS: We assessed the effects of tested drugs in subinhibitory concentrations phenotypically on the virulence factors and genotypically on the virulence encoding genes' expressions. The protection of tested drugs on S. marcescens pathogenesis was performed in vivo. Molecular docking study has been conducted to evaluate the interference capabilities of tested drugs to the SmaR QS receptor. RESULTS: Vildagliptin reduced the expression of virulence encoding genes but did not show in vitro or in vivo anti-virulence activities. Metformin reduced the expression of virulence encoding genes and inhibited bacterial virulence in vitro but did not show in vivo protection. Sitagliptin significantly inhibited virulence factors in vitro, reduced the expression of virulence factors and protected mice from S. marcescens. Docking study revealed that sitagliptin is more active than metformin and fully binds to SmaR receptor, whereas vildagliptin had single interaction to SmaR. CONCLUSION: The downregulation of virulence genes was not enough to show anti-virulence activities. Hindering of QS receptors may play a crucial role in diminishing bacterial virulence.

Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology.

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.