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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.

Bacterial infections emerge as a significant contributor to mortality and morbidity worldwide. Emerging extended-spectrum b-lactamase (ESBL) Escherichia coli strains provide a greater risk of bacteremia and mortality, are increasingly resistant to antibiotics, and are a major producer of ESBLs. E. coli bacteremialinked mastitis is one of the most common bacterial diseases in animals, which can affect the quality of the milk and damage organ functions. There is an elevated menace of treatment failure and recurrence of E. coli bacteremia necessitating the adoption of rigorous alternative treatment approaches. In this study, Se-Boil-CuO multimetallic nanoparticles (MMNPs) were synthesized as an alternate treatment from Talaromyces haitouensis extract, and their efficiency in treating ESBL E. coli was confirmed using standard antimicrobial assays. Scanning electronmicroscopy, UV--visible spectroscopy, and dynamic light scattering were used to validate and characterize themycosynthesized Se-BiO-CuOMMNPs. UV--visible spectra of Se- BiO-CuO MMNPs showed absorption peak bands at 570, 376, and 290 nm, respectively. The average diameters of the amorphous-shaped Se-BiO-CuO MMNPs synthesized by T. haitouensis extract were approximately 66--80 nm, respectively. Se-BiO-CuO MMNPs (100 mg/mL) showed a maximal inhibition zone of 18.33 ± 0.57 mm against E. coli. Se-BiO-CuO MMNPs also exhibited a deleterious impact on E. coli killing kinetics, biofilm formation, swimming motility, efflux of cellular components, and membrane integrity. The hemolysis assay also confirms the biocompatibility of Se-BiO-CuO MMNPs at the minimum inhibitory concentration (MIC) range. Our findings suggest that Se-BiO-CuO MMNPs may serve as a potential substitute for ESBL E. coli bacteremia. [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]

Background: Multidrug resistant MDR bacterial strains are causing fatal infections, such as mastitis. Thus, there is a need for the development of new target-oriented antimicrobials. Nanomaterials have many advantages over traditional antibiotics, including improved stability, controlled antibiotic release, targeted administration, enhanced bioavailability, and the use of antibiotic-loaded nanomaterials, such as the one herein reported for the first time, appear to be a promising strategy to combat antibiotic-resistant bacteria. The use of rationally designed metallic nanocomposites, rather than the use of single metallic nanoparticles (NPs), should further minimize the bacterial resistance. Aim: Green synthesis of a multimetallic/ternary nanocomposite formed of silver (Ag), titanium dioxide (TiO2), and iron(III) oxide (Fe2O3), conjugated to chitosan (CS), in which the large spectrum fluoroquinolone antibiotic ciprofloxacin (CIP) has been encapsulated. Methods: The metallic nanoparticles (NPs) Ag NPs, TiO2 NPs, and Fe2O3 NPs were synthesized by reduction of Moringa concanensis leaf aqueous extract. The ternary junction was obtained by wet chemical impregnation technique. CIP was encapsulated into the ternary nanocomposite Ag/TiO2/Fe2O3, followed by chitosan (CS) conjugation using the ionic gelation method. The resulting CS-based nanoparticulate drug delivery system (NDDS), i.e., CIP-Ag/TiO2/Fe2O3/CS, was characterized in vitro by gold standard physical techniques such as X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy. Pharmacological analyses (i.e., LC, EE, ex-vivo drug release behavior) were also assessed. Further, biological studies were carried out both ex vivo (i.e., by disk diffusion method (DDM), fluorescence-activated single cell sorting (FACS), MTT assay) and in vivo (i.e., antibacterial activity in a rabbit model, colony-forming unit (CFU) on blood agar, histopathological analysis using H&E staining). Results: The encapsulation efficiency (EE) and the loading capacity (LC) of the NDDS were as high as 94% ± 1.26 and 57% ± 3.5, respectively. XRD analysis confirmed the crystalline nature of the prepared formulation. FESEM revealed nanorods with an average diameter of 50–70 ± 12 nm. FTIR confirmed the Fe-O-Ti-CS linkages as well as the successful encapsulation of CIP into the NDDS. The zeta potential (ZP) of the NDDS was determined as 85.26 ± 0.12 mV. The antimicrobial potential of the NDDS was elicited by prominent ZIs against MDR E. coli (33 ± 1.40 mm) at the low MIC of 0.112 μg/mL. Morphological alterations (e.g., deformed shape and structural damages) of MDR pathogens were clearly visible overtime by FESEM after treatment with the NDDS at MIC value, which led to the cytolysis ultimately. FACS analysis confirmed late apoptotic of the MDR E. coli (80.85%) after 6 h incubation of the NDDS at MIC (p < 0.05 compared to untreated MDR E. coli used as negative control). The highest drug release (89% ± 0.57) was observed after 8 h using PBS medium at pH 7.4. The viability of bovine mammary gland epithelial cells (BMGE) treated with the NDDS remained superior to 90%, indicating a negligible cytotoxicity (p < 0.05). In the rabbit model, in which infection was caused by injecting MDR E. coli intraperitoneally (IP), no colonies were detected after 72 h of treatment. Importantly, the histopathological analysis showed no changes in the vital rabbit organs in the treated group compared to the untreated group. Conclusions: Taken together, the newly prepared CIP-Ag/TiO2/Fe2O3/CS nanoformulation appears safe, biocompatible, and therapeutically active to fight MDR E. coli strains-causing mastitis. [ABSTRACT FROM AUTHOR]

This study is planned to synthesise new biocompatible, nano antimicrobial formulation against biofilm producing strains. Aqueous root extract of Arctium lappa l. was used to synthesise ceria nanoparticles (CeO2 ‐NPs). The synthesised nanoparticles were encapsulated with nano‐chitosan by sol–gel method and characterised using standard techniques. Gas chromatography‐mass spectrometer of Arctium lappa l. revealed the presence of ethanol, acetone, 1‐ propanol, 2‐methylethane, 1,1‐di‐ethoxy, 1‐Butanol, and oleic acid acted as reducing and surface stabilising agents for tailoring morphology of CeO2 ‐NPs. Erythrocyte integrity after treatment with synthesised nanomaterials was evaluated by spectrophotometer measurement of haemoglobin release having biocompatibility. Scanning electron microscopy revealed the formation of mono dispersed beads shaped particles with mean particle size of 26.2 nm. X‐ray diffractometry revealed cubic crystalline structure having size of 28.0 nm. After encapsulation by nano‐chitosan, the size of CeO2 ‐NPs enhances to 48.8 nm making average coverage of about 22.6 nm. The synthesised nanomaterials were found effective to disrupt biofilm of S. aureus and P. aeruginosa. Interestingly, encapsulated CeO2 ‐NPs revealed powerful antibacterial and biofilm disruption activity examined by fluorescent live/dead staining using confocal laser scanning microscopy. The superior antibacterial activities exposed by encapsulated CeO2 ‐NPs lead to the conclusion that they could be useful for controlling biofilm producing multidrug resistance pathogens. [ABSTRACT FROM AUTHOR]

Treatment of pandrug resistant (PDR) Escherichia coli strain is the leading causative agent of bovine mastitis worldwide. Hence, becoming a potential threat to veterinary and public health. Therefore, to control the infection new nontoxic, biocompatible antimicrobial formulation with enhanced antibacterial activity is massively required. Current study was planned to synthesize chitosan coated titanium dioxide nanoparticles (CS-NPs coated TiO2). Coating was being done by chitosan nanoparticles (CS-NPs) using ionic gelation method. Aqueous solution of Moringa concanensis leaf extract was used to synthesize titanium dioxide nanoparticles (TiO2 NPs). The synthesized nanoformulations were characterized by using XRD, SEM, and FTIR. X-ray diffraction (XRD) analysis indicated the crystalline phase of TiO2 NPs and CS-NPs coated TiO2 NPs. Scanning Electron Microscopy (SEM) confirmed spherical shaped nanoparticles size of chitosan NPs ranging from 19–25 nm and TiO2 NPs 35–50 nm. Thesize of CS-NPs coated TiO2 NPs was in the range of 65–75 nm. The UV-Vis Spectra and band gap values illustrated the red shift in CS-NPs coated TiO2 NPs. Fourier transform infrared (FTIR) spectroscopy confirmed the linkages between TiO2 NPs and chitosan biopolymer, Zeta potential confirmed the stability of CS-NPs coated TiO2 NPs by showing 95 mV peak value. In-vitro antibacterial activity of CS-NPs coated TiO2 NPs and Uncoated TiO2 NPs was evaluated by disc diffusion method against PDR strain of E. coli isolated from mastitic milk samples. The antibacterial activity of all the synthesized nanoformulations were noted and highest antibacterial activity was shown by CS-NPs coated TiO2-NPs against pandrug resistant (PDR) E. coli strain with the prominent zone of inhibition of 23 mm. Morphological changes of E. coli cells after the treatment with MIC concentration (0.78 μg/ml) of CS-NPs coated TiO2 NPs were studied by transmission electron microscopy TEM showedrigorous morphological defectand has distorted the general appearance of the E. coli cells. Cytotoxicity (HepG2 cell line) and hemolytic (human blood) studies confirmed nontoxic/biocompatible nature of CS-NPs coated biologically synthesized TiO2 NPs. The results suggested that biologically synthesized and surface modified TiO2 NPs by mucoadhesive polysaccharides (e.g. chitosan) coating would be an effective and non-toxic alternative therapeutic agent to be used in livestock industry to control drug resistant veterinary pathogens. [ABSTRACT FROM AUTHOR]

The silver oxide nanoparticles (AgO2 ‐NPs) were synthesised using silver foil as a new precursor in wet chemical method. X‐ray diffraction analysis shows crystallographic structures of AgO2 ‐NPs with crystallite size of 35.54 nm well‐matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical‐shaped nanoparticles. Energy dispersive X‐ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra‐red analysis confirmed the formation of AgO2 ‐NPs with the presence of Ag‐O‐Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO2 ‐NPs. This study also described the effect of AgO2 ‐NPs having synergistic activity with β lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli). Among isolated strains of E. coli, 60.0% were found to be ESBL producer. The synergistic activities of AgO2 ‐NPs with ceftriaxone suggest that these combinations are effective against MDR‐ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR‐ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO2 ‐NPs synergistic effect can be used as an efficient approach to combat uro‐pathogenic infections. [ABSTRACT FROM AUTHOR]

An antifungal compound 9, 10-dihydrophenanthrene - 2 - carboxylic acid was isolated from a marine derived bacterium Pseudomonas putida isolated from surface water samples of Karachi fish harbor coast line. The structure was explored using extensive ID- and 2D-NMR spectroscopic techniques. The compound was found to be active against fungal strains obtained from clinical samples whereas strong activity was noted against Candida albicans with a MIC value of 20μg/ml, as the purified compound showed promising anticandidal activity a multidisciplinary approach is needed to explore further this compound as potential pharmacological lead compound against Candida spp and will add in the global hunt for clinically functional antifungal agents. [ABSTRACT FROM AUTHOR]

Bacterial resistance is spreading globally due to excessive use of antibiotics, making it one of our times biggest challenges. To address this issue present study was conducted to evaluate the antibacterial activity of copper oxide nanoparticles against methicillin-resistant S. aureus (MRSA). Copper oxide nanoparticles were synthesized by chemical precipitation method and were characterized by UV-Visible, FT-IR spectroscopy, X-ray diffraction (XRD) and Scanning Electron Microscopy. These nanoparticles of 27nm were assessed for antibacterial activity using disc diffusion method. Our results showed superb inhibitory effects of CuO nanoparticles with increase in concentration and complete inhibition was recorded against tested strains of S. aureus at 100μl/ml and 125μl/ml concentration. The study concludes that the drugs which do not show any inhibitory effects against resistant bugs could be augmented with CuO nanoparticles to achieve the treatment goal. [ABSTRACT FROM AUTHOR]

The emergence of multi drug resistant microbial pathogens has become a global health challenge and set a dire requirement of searching new effective antimicrobials. Soil is an ultimate reservoir of biologically active micro flora, which harbors trillions of microbial strains producing compounds of commercial interest. Hence aim of the present study was an attempt to isolate and identify the antibiotic producing microbial strains from the red soil of Himalayan an unexplored region of Pakistan. In this study from 10 different soil samples only one bacterial strain was isolated capable of antimicrobial activity. Strain was identified by biochemical characteristics and final identification was done by API 20 NE kit which showed 99% homology with P. aeruginosa. Hence the strain was identified as P. aeruginosa S2. Antibacterial and antifungal activity of the P. aeruginosa S2 showed that Staphylococcus aureus was extremely sensitive to it with a zone of inhibition of 42mm. Staphylococcus epidermidis, Enterobacter aerogenes, Aspergillus fumigatus and Candida albicans were also inhibited by the isolated strain. Effect of Glycerol, Copper sulphate (CuSo4), Sodium sulphate (Na2SO4) and Glycerol on antibiotic production was also evaluated by supplementing growth media with these chemicals. Pseudomonas aeruginosa was grown in bulk quantity using solid state fermentation and crude extract was prepared using organic solvents and subjected to silica gel column chromatography for purification of active compound. Purified compound showed antibacterial against human pathogens. The unexplored Kashmir Himalayas are of great significance because of its richness in biodiversity and need to be explored for isolation and characterization of native microbes for biologically active secondary metabolites. This un touched region may be considered as hub of new antimicrobials and may have applications in natural product-based drug discovery. [ABSTRACT FROM AUTHOR]

This study was planned in order to investigate effective essential oils to inhibit in-vitro growth of Methicillin resistant Staphylococcus aureus (MRSA). In this study using disc diffusion method anti MRSA activity of ten diverse essential oils extracted from traditional plants namely Thymus vulgaris L, Mentha pulegium, Ocimum sanctum, Mentha piperita, Cymbopogon citratus, Rosmarinus officinalis L., Cortex cinnamom, Citrus nobilis x Citrus deliciosa, Origanum vulgare and Mentha sp. was examined. All the essential oils inhibited growth of S. aureus to different extent, by exhibiting moderate to elevated zones of inhibitions. Essential oils of cinnamon (Cortex cinnamomi) and thyme (Thymus vulgaris L) were observed to be the most powerful against MRSA strains used in this study. At lowest concentration of 25μl/ml essential oils comprehensible zone of inhibition was found 9±0.085mm and 8±0.051mm respectively, and at elevated concentrations there was a total decline in growth of MRSA and a very clear zone of inhibition was observed. A synergistic effect of essential oils in amalgamation with amoxicillin a Penicillin group of antibiotic was also examined. Interestingly a strong synergism was observed with oregano (Origanum vulgare) and pennyroyal mint (Mentha pulegium) essential oils, which were not so effective alone driven out to be important synergistic candidate. Our results demonstrated that essential oils of cinnamon and thyme can be used as potential antimicrobial agent against the Methicillin-resistant Staphylococcus aureus infections and Amoxicillin antibacterial activity can be enhanced using active constituents present in oregano and pennyroyal mint essential oils. [ABSTRACT FROM AUTHOR]

Farid Menaa was not included as an author in the published article [[1]]. Author Contributions Conceptualization, B.U.; and N.Z.; methodology, M.B.K.N.; software, S.S.; and A.B.; validation, G.S. and W.U.-N.; formal analysis, F.M.; N.J.; investigation, N.Z.; and F.M.; resources, S.S.; and A.B.; data interpretation, N.Z.; and F.M.; writing - original draft preparation, N.Z.; review and editing, B.U.; and F.M.; visualization, M.B.K.N.; and W.U.-N.; supervision, B.U.; project administration, M.B.K.N. All authors have read and agreed to the published version of the manuscript. The corrected Author Contributions Statement appears here. [Extracted from the article]

To improve the efficacy of existing classes of antibiotics (ciprofloxacin), allow dose reduction, and minimize related toxicity, this study was executed because new target-oriented livestock antimicrobials are greatly needed to battle infections caused by multidrug-resistant (MDR) strains. The present study aims to green synthesize a biocompatible nanohybrid of ciprofloxacin (CIP)-Ag/TiO2/chitosan (CS). Silver and titanium nanoparticles were green synthesized using Moringa concanensis leaves extract. The incorporation of silver (Ag) nanoparticles onto the surface of titanium oxide nanoparticles (TiO2NPs) was done by the wet chemical impregnation method, while the encapsulation of chitosan (CS) around Ag/TiO2 conjugated with ciprofloxacin (CIP) was done by the ionic gelation method. The synthesized nanohybrid (CIP-Ag/TiO2/CS) was characterized using standard techniques. The antibacterial potential, killing kinetics, cytotoxicity, drug release profile, and minimum inhibitory concentration (MIC) were determined. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) revealed spherical agglomerated nanoparticles (NPs) of Ag/TiO2 with particle sizes of 47–75 nm, and those of the CIP-Ag/TiO2/CS nanohybrid were in range of 20–80 nm. X-ray diffractometer (XRD) patterns of the hetero system transmitted diffraction peaks of anatase phase of TiO2 and centered cubic metallic Ag crystals. Fourier Transform Infrared spectroscopy (FTIR) confirmed the Ti-O-Ag linkage in the nanohybrid. The zeta potential of CIP-Ag/TiO2/CS nanohybrid was found (67.45 ± 1.8 mV), suggesting stable nanodispersion. The MIC of CIP-Ag/TiO2/CS was 0.0512 μg/mL, which is much lower than the reference value recorded by the global CLSI system (Clinical Laboratory Standards Institute). The CIP-Ag/TiO2/CS nanohybrid was found to be effective against mastitis causing MDR E. coli; killing kinetics showed an excellent reduction of E. coli cells at 6 h of treatment. Flow cytometry further confirmed antibacterial potential by computing 67.87% late apoptosis feature at 6 h of treatment; antibiotic release kinetic revealed a sustained release of CIP. FESEM and TEM confirmed the structural damages in MDR E. coli (multidrug-resistant Escherichia coli). The CIP-Ag/TiO2/CS nanohybrid was found to be biocompatible, as more than 93.08% of bovine mammary gland epithelial cells remained viable. The results provide the biological backing for the development of nanohybrid antibiotics at a lower MIC value to treat infectious diseases of cattle and improve the efficacy of existing classes of antibiotics by conjugation with nanoparticles. [ABSTRACT FROM AUTHOR]

The silver oxide nanoparticles (AgO 2 -NPs) were synthesised using silver foil as a new precursor in wet chemical method. X-ray diffraction analysis shows crystallographic structures of AgO 2 -NPs with crystallite size of 35.54 nm well-matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical-shaped nanoparticles. Energy dispersive X-ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra-red analysis confirmed the formation of AgO 2 -NPs with the presence of Ag-O-Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO 2 -NPs. This study also described the effect of AgO 2 -NPs having synergistic activity with β lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli) . Among isolated strains of E. coli , 60.0% were found to be ESBL producer. The synergistic activities of AgO 2 -NPs with ceftriaxone suggest that these combinations are effective against MDR-ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR-ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO 2 -NPs synergistic effect can be used as an efficient approach to combat uro-pathogenic infections.

Since ancient times, natural products from plants, animals, microbial and marine sources have been exploited for treatment of several diseases. The knowledge of our ancestors is the base of modern drug discovery process. However, due to the presence of extensive biodiversity in natural sources, the percentage of secondary metabolites screened for bioactivity is low. This review aims to provide a brief overview of historically significant natural therapeutic agents along with some current potential drug candidates. It will also provide an insight into pros and cons of natural product discovery and how development of recent approaches has answered the challenges associated with it.