Dual Drug-Loaded Coaxial Nanofiber Dressings for the Treatment of Diabetic Foot Ulcer.

Introduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization. Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds. Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups. Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing.

Background: Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. Rationale: In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. Results: The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. Conclusion: This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

Green Synthesis of Silver Nanoparticles Using Jacobaea maritima and the Evaluation of Their Antibacterial and Anticancer Activities.

Much attention has been gained on green silver nanoparticles (green-AgNPs) in the medical field due to their remarkable effects against multi-drug resistant (MDR) microorganisms and targeted cancer treatment. In the current study, we demonstrated a simple and environment-friendly (i.e., green) AgNP synthesis utilizing Jacobaea maritima aqueous leaf extract. This leaf is well-known for its medicinal properties and acts as a reducing and stabilizing agent. Nanoparticle preparation with the desired size and shape was controlled by distinct parameters; for instance, temperature, extract concentration of salt, and pH. The characterization of biosynthesized AgNPs was performed by the UV-spectroscopy technique, dynamic light scattering, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. The successful formation of AgNPs was confirmed by a surface plasmon resonance at 422 nm using UV-visible spectroscopy and color change observation with a particle size of 37± 10 nm and a zeta potential of -10.9 ± 2.3 mV. SEM further confirmed the spherical size and shape of AgNPs with a size varying from 28 to 52 nm. Antibacterial activity of the AgNPs was confirmed against all Gram-negative and Gram-positive bacterial reference and MDR strains that were used in different inhibitory rates, and the highest effect was on the E-coli reference strain (MIC = 25 µg/mL). The anticancer study of AgNPs exhibited an IC50 of 1.37 µg/mL and 1.98 µg/mL against MCF-7 (breast cancer cells) and A549 (lung cancer cells), respectively. Therefore, this green synthesis of AgNPs could have a potential clinical application, and further in vivo study is required to assess their safety and efficacy.

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia.

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic 'Umrah' ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia.

Liposome-Encapsulated Tobramycin and IDR-1018 Peptide Mediated Biofilm Disruption and Enhanced Antimicrobial Activity against Pseudomonas aeruginosa.

The inadequate eradication of pulmonary infections and chronic inflammation are significant complications in cystic fibrosis (CF) patients, who usually suffer from persistent and frequent lung infections caused by several pathogens, particularly Pseudomonas aeruginosa (P. aeruginosa). The ability of pathogenic microbes to protect themselves from biofilms leads to the development of an innate immune response and antibiotic resistance. In the present work, a reference bacterial strain of P. aeruginosa (PA01) and a multidrug-resistant isolate (MDR 7067) were used to explore the microbial susceptibility to three antibiotics (ceftazidime, imipenem, and tobramycin) and an anti-biofilm peptide (IDR-1018 peptide) using the minimum inhibition concentration (MIC). The most effective antibiotic was then encapsulated into liposomal nanoparticles and the IDR-1018 peptide with antibacterial activity, and the ability to disrupt the produced biofilm against PA01 and MDR 7067 was assessed. The MIC evaluation of the tobramycin antibacterial activity showed an insignificant effect on the liposomes loaded with tobramycin and liposomes encapsulating tobramycin and IDR-1018 against both P. aeruginosa strains to free tobramycin. Nevertheless, the biofilm formation was significantly reduced (p < 0.05) at concentrations of ≥4 µg/mL and ≤32 µg/mL for PA01 and ≤32 µg/mL for MDR 7067 when loading tobramycin into liposomes, with or without the anti-biofilm peptide compared to the free antibiotic, empty liposomes, and IDR-1018-loaded liposomes. A tobramycin concentration of ≤256 µg/mL was safe when exposed to a lung carcinoma cell line upon its encapsulation into the liposomal formulation. Tobramycin-loaded liposomes could be a potential candidate for treating lung-infected animal models owing to the high therapeutic efficacy and safety profile of this system compared to the free administration of the antibiotic.

Preparation and evaluation of benzalkonium chloride hand sanitizer as a potential alternative for alcohol-based hand gels.

Hand hygiene is one of the effective measures for reducing the transmission of infections. Alcohol-based hand sanitizers containing ethanol or isopropanol are considered efficient alternatives to handwashing with water and soap. Despite being effective against a broad-spectrum of microbes, fining an effective alternative to the alcohol-based hand sanitizers became a necessity owning to the limitations associated with their use, such as skin dryness, irritant contact dermatitis, and intoxication upon their accidental ingestion. Furthermore, in certain circumstances when the demand for alcohol exceeds the supply, like in the current COVID19 pandemic, formulating an effective non-alcoholic hand sanitizer would be a potential solution. Therefore, in this study, a non-alcoholic hand sanitizer containing benzalkonium chloride (BKC) as an active ingredient was prepared and evaluated as a less irritant and more persistent hand sanitizer gel. The hand gel was characterized by pH, viscosity, and spreadability. Results showed that this product has low viscosity, high spreadability and pH of 6.3, which is less likely to cause skin irritation. The antibacterial assessment (zone of inhibition) of the BKC-based hand sanitizer demonstrated antibacterial activities against nine out of eleven gram-positive and gram-negative bacterial strains, while the acceptability study on ten participants showed no signs of skin irritation nor redness upon its application. Consequently, this non-alcoholic based hand sanitizer is suggested as a potential alternative to alcohol-based hand gels.

Formulation and Evaluation of Alcohol-Free Hand Sanitizer Gels to Prevent the Spread of Infections during Pandemics.

Hand hygiene is an essential factor to prevent or minimize the spread of infections. The ability to prepare an alcohol-free hand sanitizer (AFHS) with antimicrobial properties is crucial, especially during pandemics, when there are high demands and a low supply chain for ethanol and isopropanol. The objective of this study was to prepare AFHS gels based on natural materials that contain essential oils (EOs) that would be effective against a broad spectrum of pathogens. The results showed that the organoleptic characteristics of all prepared hand sanitizer gels were considered acceptable. The pH of the formulations was slightly acidic (circa 3.9) owing to the presence of aloe vera in large proportions (90% v/v), which is known for its acidity. The spreadability for all tested formulations was in the acceptable range. The antimicrobial effectiveness test demonstrated that the prepared hand sanitizer gels had antimicrobial activities against different gram-positive and gram-negative bacteria and Candida albicans yeast. The highest antibacterial effect was observed with tea tree oil hand sanitizers, which lack activity against the yeast, while clove oil hand sanitizers showed effectiveness against all microorganisms, including Candida albicans. The lavender hand sanitizer exhibited the least antimicrobial efficiency. The acceptability study on 20 human volunteers showed that the hand sanitizer gel containing 1.25% (v/v) clove oil did not produce any signs of skin irritation. This study suggested that the prepared natural hand sanitizer gel with 1.25% (v/v) clove oil can be a potential alternative to commonly used alcohol-based hand sanitizers (ABHS).

The Delivery of the Novel Drug 'Halicin' Using Electrospun Fibers for the Treatment of Pressure Ulcer against Pathogenic Bacteria.

Pressure ulcer or bedsore is a form of skin infection that commonly occurs with patients admitted to the hospital for an extended period of time, which might lead to severe complications in the absence of medical attention, resulting in infection either by drug-sensitive or drug-resistant bacteria. Halicin, a newly discovered drug effective against several bacterial strains, including multidrug-resistant bacteria, was investigated to reduce bacterial infection burden. This study aims to formulate halicin into electrospun fibers to be applied in bedsores as antibacterial dressing to assess its efficacy against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli and Acinetobacter baumannii) by studying the minimum inhibitory concentration (MIC) and bacterial zone of inhibition assays. The diameters of inhibition growth zones were measured, and the results have shown that the drug-loaded fibers were able to inhibit the growth of bacteria compared to the halicin discs. The release profile of the drug-loaded fibers exhibited a complete release of the drug after 2 h. The results demonstrated that the drug-loaded fibers could successfully release the drug while retaining their biological activity and they may be used as a potential antimicrobial dressing for patients with pressure ulcers caused by multidrug resistant bacteria.