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Multidrug-resistant wound infections are a global health threat and a leading cause of death, persisting despite available treatments due to antibiotic resistance, biofilms, and ineffective drug delivery systems. The aim of this study is to (i) formulate an innovative nano-drug delivery system (NDDS) based on a Carbopol nanoemulgel (NEG) co-loaded with neomycin-silver/zinc oxide nanocomposite (NC) that could fight clinical MDR and treat biofilm-forming wound pathogens through topical application, and (ii) assess its in vivo wound-healing potential. The silver/zinc oxide (Ag/ZnO) NC was synthesized by co-inoculating the metabolites of Aspergillus welwitschiae and Meyerozyma guilliermondii. The synthesized NC was then conjugated with neomycin and loaded into a Carbopol NEG for efficient topical delivery. The resulting Neo-Ag/ZnO NEG was characterized physicochemically (e.g., UV-visible [UV-Vis] spectrophotometry, field emission scanning electron microscopy, X-ray diffraction, and Fourier transform infrared [FTIR] spectroscopy), biologically (e.g., in vitro antimicrobial, antibiofilm, and hemolytic activities), and pharmacologically (e.g., drug content, ex vivo drug release behavior, and in vivo wound-healing potential). The physicochemical analysis confirmed the successful mycosynthesis of the Carbopol NEG-loaded Neo-Ag/ZnO NC. SEM depicted a crystalline polyhedral shape of the small NC (average particle size of 38 nm). FTIR studies showed a slight interaction with the drug and other bioactive moieties in the Carbopol NEG. The Neo content in the Carbopol NEG was as high as 98%, and a maximum release of 81% for Neo, Ag, and ZnO ions was noticed after 12 h. The NDDS appeared hemocompatible and displayed a minimal inhibition concentration of 0.002 µg/mL with the greatest antimicrobial potential against S. aureus (an inhibition zone of 46 mm) compared to other tested wound microbes (p < 0.05). Statistically significant wound-healing activity was found for NDDS (p = 0.0001) in comparison to the control at a concentration of 100 mg/mL. The results showed that this newly developed Carbopol NEG-loaded neo-Ag/ZnO NC appeared promising for controlling resistant skin infections and boosting wound regeneration.

Introduction: Gestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases. Methods: The current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated. Results: It was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group. Discussion: The results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM. [ABSTRACT FROM AUTHOR]

Background: Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR. To address this, we investigated the effect of GLP-1RA-based treatment strategies on TIR among patients with T2DM in real-world clinical practice. Methods: This multicenter, retrospective, real-world study included patients with T2DM who had previously used a continuous glucose monitoring (CGM) system and received treatment with GLP-1RAs or oral antidiabetic drugs (OADs). Patients who received OADs served as controls and were matched in a 1:1 ratio to their GLP-1RA counterparts by propensity score matching. The primary endpoint was the TIR after 3–6 months of treatment. Results: According to propensity score matching, 202 patients were equally divided between the GLP-1RA and OAD groups. After 3–6 months of treatment, the TIR values for the GLP-1RA and OAD groups were 76.0% and 65.7%, respectively (p < 0.001). The GLP-1RA group displayed significantly lower time above range (TAR) and mean glucose values than the OAD group (p < 0.001). Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3–6 months of treatment (p < 0.05). Conclusion: These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA. [ABSTRACT FROM AUTHOR]

Biogenic methods are an effective alternative to chemical methods in the preparation of nanoparticles. Our study used Crocus caspius extract to synthesize gold nanoparticles (CC-AuNPs) in a green manner. The eco-friendly synthesis of AuNPs was conducted by optimizing the temperature and concentration of HAuCl4 and extract. Synthesized CC-AuNPs were characterized using TEM, SEM, EDX, XRD, FTIR, and UV–Vis spectroscopy. The prepared CC-AuNPs were detected with a size of around 22.66 ± 1.67 nm. The FT-IR analysis of the biomolecules involved in synthesizing CC-AuNPs was performed. Additionally, these biomolecules capped on the AuNPs were revealed by TG/DTA analysis. The EDX study demonstrated the existence of elemental gold. The biosynthesized CC-AuNPs were effectively applied as green catalysts to reduce three organic pollutant dyes—methyl orange (MO), methylene blue (MB), and 4-nitrophenol. In the biological evaluations, the free radical scavenging activity of the eco-friendly CC-AuNPs (DPPH assay) indicated an IC50 value of 29.22 ± 0.47 µg/mL. They displayed effective antibacterial activity against several bacterial strains. Their anticancer activity against AGS and MCF-7 cells showed IC50 concentrations at 48.2 µg/mL and 51.76 µg/mL, respectively. Furthermore, CC-AuNPs presented excellent antileishmanial activity (IC50 = 13.92 µg/mL). Therefore, the green AuNPs are efficient in biomedicine and nanobiotechnology. [ABSTRACT FROM AUTHOR]

Urticaria affects all age groups of a population. It is triggered by allergens in foods, insect bites, medications, and environmental conditions. Urticaria is characterized by itching, a burning sensation, wheals and flares, erythema, and localized edema. The aim of this study was to develop a polymeric dosage form of ebastine using Carbopol 940 and mixture of span and tween. The emulsion was prepared, the gelling agent was added and the desired emulgel loaded with active drug was formulated. The formulations were subjected to physical stability, pH, viscosity, spreadability, drug content analysis, thermal analysis, in vitro drug release, and in vivo anti-allergic activity in animal model. The formulated emulgel exhibited good physical stability. The pH of the formulation was in the range of 5.2 ± 0.17 to 5.5 ± 0.20 which is suitable for topical application. Insignificant changes (p>.05) were observed in viscosity and spreadability of stored emulgels. The drug content was in the official limit of Pharmacopeia (i.e. 100 ± 10%). DSC measurements predicted that there is no interaction between the active moiety and excipients in emulgel formulation. The optimized formulation (ES3) released 74.25 ± 1.8% of ebastine after 12 h. The ebastine emulgel showed significant (p<.05; ANOVA) in vivo anti-allergic activity as compared to commercial product BenadrylVR in histamine-induced allergy in rabbits. This study concluded that a topical drug delivery of ebastine-loaded emulgel could be well tolerated and safe for the treatment of urticaria/hives. [ABSTRACT FROM AUTHOR]

Current research aimed to develop nanocubosomes co-loaded with dual anticancer drugs curcumin and temozolomide for effective colon cancer therapy. Drugs co-loaded nanocubosomal dispersion was prepared by modified emulsification method using glyceryl monooleate (GMO), pluronic F127 and bovine serum albumin (BSA) as a lipid phase, surfactant, and stabilizer, respectively. The resulting nanocubosomes were characterized by measuring hydrodynamic particle size, particle size distribution (PSD), drug loading capacity (DL), encapsulation efficiency (EE), colloidal stability and drug release profile. We also physiochemically characterized the nanocubosomes by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and x-rays diffraction (XRD) for their morphology, polymer drug interaction and its nature, respectively. Further, the in-vitro cell-uptake, mechanism of cell-uptake, in-vitro anti-tumor efficacy and apoptosis level were evaluated using HCT-116 colon cancer cells. The prepared nanocubosomes exhibited a small hydrodynamic particle size (PS of 150 ± 10 nm in diameter) with nearly cubic shape and appropriate polydispersity index (PDI), enhanced drug loading capacity (LC of 6.82 ± 2.03% (Cur) and 9.65 ± 1.53% (TMZ), high entrapment efficiency (EE of 67.43 ± 2.16% (Cur) and 75.55 ± 3.25% (TMZ), pH-triggered drug release profile and higher colloidal stability in various physiological medium. Moreover, the nanocubosomes showed higher cellular uptake, in-vitro cytotoxicity and apoptosis compared to free drugs, curcumin and temozolomide, most likely because its small particle size. In addition, BSA-stabilized nanocubosomes were actively taken by aggressive colon cancer cells that over-expressed the albumin receptors and utilized BSA as nutrient source for their growth. In short, this study provides a new and simple strategy to improve the efficacy and simultaneously overawed the adaptive treatment tolerance in colon cancer. [ABSTRACT FROM AUTHOR]

It is important to create new generations of materials that can destroy multidrug-resistant bacterial strains, which are a serious public health concern. This study focused on the biosynthesis of an essential oil entrapped in titanium dioxide (TiO2) calcium alginate-based microspheres. In this research, calcium alginate-based microspheres with entrapped TiO2 nanoparticles and cinnamon essential oil (CI-TiO2-MSs) were synthesized, using an aqueous extract of Nigella sativa seeds for TiO2 nanoparticle preparation, and the ionotropic gelation method for microsphere preparation. The microspheres obtained were spherical, uniformly sized, microporous, and rough surfaced, and they were fully loaded with cinnamon essential oil and TiO2 nanoparticles. The synthesized microspheres were analyzed for antibacterial activity against the clinical multidrug-resistant strain of Staphylococcus aureus. Disc diffusion and flow cytometry analysis revealed strong antibacterial activity by CI-TiO2-MSs. The synthesized CI-TiO2-MSs were characterized by the SEM/EDX, X-ray diffraction, and FTIR techniques. Results showed that the TiO2 nanoparticles were spherical and 99 to 150 nm in size, whereas the CI-TiO2-MSs were spherical and rough surfaced. Apoptosis analysis and SEM micrography revealed that the CI-TiO2-MSs had strong bactericidal activity against S. aureus. The in vitro antibacterial experiments proved that the encapsulated CI-TiO2-MSs had strong potential for use as a prolonged controlled release system against multidrug-resistant clinical S. aureus. [ABSTRACT FROM AUTHOR]