Electrospun PCL/PVA/PHMB nanofibers incorporating Ziziphus jujuba fruit extract as promising wound dressings with potent antibacterial and antidiabetic properties.

This investigation examined the potential antibacterial and antidiabetic effects of wound dressings created using electrospun nanofibers containing Ziziphus jujuba fruit extract (ZJ). These nanofibers were composed of a combination of Polycaprolactone (PCL), Polyvinyl Alcohol (PVA), and Polyhexamethylene Biguanide (PHMB). The process of creating these nanofibers involved electrospinning. The nanofiber products, which included PCL, PCL/PVA, PCL/PVA/ZJ, PCL/PVA/PHMB, and PCL/PVA/PHMB/ZJ, underwent a morphology, physicochemical, and biological assessment. Incorporating PHMB into the nanofibers enhanced the antibacterial properties, effectively preventing bacterial infections in wounds. Furthermore, including ZJ fruit extract in the nanofibers provided antidiabetic properties, making these dressings suitable for diabetic patients. The PCL/PVA/PHMB/ZJ combination exhibited exceptional healing capabilities and superior antibacterial efficiency in MRSA-infected wounds. The histological assay confirmed complete wound healing by day 14, accompanied by reduced inflammation. Based on these findings, using PCL/PVA/PHMB/ZJ as innovative wound dressings is recommended, as they can expedite wound healing while offering significant antidiabetic and antibacterial features. Ultimately, these electrospun nanofibers possess the potential to serve as advanced wound dressings with enhanced antibacterial and anti-diabetes properties.

Efficacy and Safety of Preoperative Prophylaxis in Cataract Surgery with Combined Topical Antiseptics: A Microbiological Study.

INTRODUCTION: To evaluate the antimicrobial efficacy of an ophthalmic formulation containing hexamidine diisethionate (HD) 0.05%, polyhexamethylene biguanide (PHMB) 0.0001%, and edetate disodium (EDTA) 0.01% (Keratosept®, Bruschettini, Genova, Italy) on the microbial flora of a healthy ocular surface. METHODS: Patients were enrolled consecutively. Each patient applied two drops of Keratosept® in the eye scheduled for cataract surgery (study eye) three times daily in the 2 days prior to surgery and one time in the morning of surgery. The contralateral eyes were considered as control (control eye). Bilateral conjunctival swabs were collected before the first administration (T0) and the morning of surgery (T1). The swabs were processed within 3 h from sampling for the automated detection of the presence of replicating microorganisms (colony-forming units, CFU/mL) and the provision of real-time growth curves. RESULTS: Conjunctival swabs of 32 patients (n = 128) were examined. Six patients were excluded from the efficacy analysis because of microbial load < 50 CFU/mL at T0 in the study eye. No difference between study and control eyes was observed at T0 (p = 0.40). Compared with T0, 20 (76.9%) study eyes and 10 (38.5%) control eyes showed a ≥ 1 log reduction of the microbial load at T1, with a significant difference between groups (p = 0.005). Keratosept® showed good tolerability, and no adverse events or eye discomfort were recorded. CONCLUSIONS: This study showed that the low-dose combination of antiseptic agents in the Keratosept® ophthalmic solution effectively reduces the bacterial load of healthy flora on the ocular surface.

DNA/BSA Binding and Antimicrobial Properties of Biguanide-Cu(II) Complexes.

The biguanide Cu(II) complexes [Cu(L1-4)2](ClO4)2 were synthesized and spectroscopic/analytical techniques were used to clarify their structures. Single crystals of complex [Cu(L4)2](ClO4)2 was obtained and its definite structure was determined by single crystal X-ray diffraction study. The complexes [Cu(L1-4)2](ClO4)2 were screened for their FSds-DNA interactions by using UV-Vis absorption and fluorescence spectroscopies. The complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 were shown to exhibit higher affinity for binding DNA. Examining the EB-DNA interaction, it is believed that the complexes interact with DNA through a groove binding mechanism. The interaction of complexes with BSA were observed through the quenching of the fluorescence emission. Complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 show moderate binding affinity to BSA through a static mode. Additionally, the Cu(II) complexes were screened for their antibacterial activities against various bacterial strains. Complexes showed potential antimicrobial activity against Salmonella typhimurium, Bacillus cereus, Salmonella typhimurium and S. aureus.

Fabrication of antimicrobial packaging based on polyaminopropyl biguanide incorporated pectin/polyvinyl alcohol films for fruit preservation.

Pectin (PEC)/polyvinyl alcohol (PVA), plasticizers, and polyaminopropyl biguanide (Pb) (0.125%-1%) were used to prepare the film solution. The results demonstrated significantly enhanced tensile strength and elongation at break of PEC/PVA/Pb 0.25% film than PEC/PVA film. Scanning electron microscopy was carried out to investigate the continuous and dense structure of the PEC/PVA/ Pb0.25% film. FTIR, XPS, and XRD revealed that Pb addition to the PEC/PVA film matrix changed its physicochemical properties by forming new hydrogen and CN bonds. Moreover, the composite films exhibited strong antimicrobial activity against food-borne microorganisms (E. coli and S. aureus), and post-harvest pathogens (P. italicum and F. proliferatum) in vitro. The composite film effectively inhibited P. italicum growth during citrus experiments, while maintaining nutritional components (vitamin C, total flavonoid, and total polyphenol content). Overall, the antimicrobial composite film presented promising applicability in food packaging.

Biodegradable gelatin/pectin films containing cellulose nanofibers and biguanide polymers: Characterization and application in sweet cherry packaging.

To expand the utilization of gelatin and pectin derived from agricultural by-products, the composite films composed of gelatin, citrus pectin, cellulose nanofibers (CNF), and polyhexamethylene biguanide hydrochloride (PHMB) were prepared through the solvent casting method. Fourier infrared spectroscopy analysis verified the successful integration of CNF and PHMB into the gelatin-pectin matrix. The incorporation of CNF as a reinforcing agent substantially enhanced the barrier capabilities of the composite film. Moreover, the addition of PHMB, functioning as an antimicrobial agent, not only granted the film with antibacterial properties but also improved its physical characteristics and biodegradability. A water contact angle experiment revealed the film presented a certain degree of hydrophobicity. The optimal performances were attained with a composition in which CNF and PHMB constituted 8 % and 3 %, respectively, of the total weight of gelatin and pectin. As a packaging film, the composite film demonstrated its effectiveness by reducing the decay index and weight loss rate of sweet cherries during a 12-day storage period. In the soil degradation test, the composite film exhibited notable structural degradation by the 16th day. Consequently, the composite film will be used as an innovative and biodegradable packaging material to provide a sustainable solution for food packaging industries.

Management of Pediatric Superficial Partial-Thickness Burns with Polyhexamethylene Biguanide: Outcomes and Influencing Factors.

Background: In burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses the role of polyhexamethylene biguanide (PHMB) in managing pediatric superficial partial-thickness burns, focusing on the effects of various patient-specific factors on recovery. Methods: Through a retrospective analysis of 27 pediatric cases treated with PHMB, we evaluated the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the time until reepithelialization (TTRE). Results: The majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. A mean healing time of 8.78 (SD: 2.64) days was observed, with the extent of the burn showing a strong correlation (r: 0.63) to TTRE. Most treatments were managed outpatient, evidenced by a negligible average hospital stay (0.96 days), with recorded no complications. Conclusions: Our findings endorse PHMB as a promising treatment for superficial second-degree burns in young patients, due to the observed stable and rapid wound closure without the association of increased risks. Continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management is necessary. Future research should assess long-term outcomes, including functionality, scar quality, and patient satisfaction.

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD).

BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.

Safety and effectiveness of an antiseptic wound cleansing and irrigation solution containing polyhexamethylene biguanide.

OBJECTIVE: There is currently a wide range of cleansing and irrigation solutions available for wounds, many of which contain antimicrobial agents. The aim of this study was to assess the safety of HydroClean Solution (HARTMANN, Germany), a polyhexamethylene biguanide (PHMB)-containing irrigation solution, in a standard cytotoxicity assay, and to assess its effect in a three-dimensional (3D) full-thickness model of human skin. METHOD: A number of commercially available wound cleansing and irrigation solutions, including the PHMB-containing irrigation solution, were tested in a cytotoxicity assay using L929 mouse fibroblasts (ISO 10993-5:2009). The PHMB-containing irrigation solution was then assessed in an in vitro human keratinocyte-fibroblast 3D full-thickness wounded skin model to determine its effect on wound healing over six days. The effect of the PHMB-containing irrigation solution on tissue viability was measured using a lactate dehydrogenase (LDH) assay, and proinflammatory effects were measured using an interleukin-6 (IL-6) production assay. RESULTS: The PHMB-containing irrigation solution was shown to be equivalent to other commercially available cleansing and irrigation solutions when tested in the L929 fibroblast cytotoxicity assay. When assessed in the in vitro 3D human full-thickness wound healing model, the PHMB-containing irrigation solution treatment resulted in no difference in levels of LDH or IL-6 when compared with levels produced in control Dulbecco's phosphate-buffered saline cultures. There was, however, a pronounced tissue thickening of the skin model in the periwound region. CONCLUSION: The experimental data presented in this study support the conclusion that the PHMB-containing irrigation solution has a safety profile similar to other commercially available cleansing and irrigation solutions. Evidence also suggests that the PHMB-containing irrigation solution does not affect tissue viability or proinflammatory cytokine production, as evidenced by LDH levels or the production of IL-6 in a 3D human full-thickness wound healing model. The PHMB-containing irrigation solution stimulated new tissue growth in the periwound region of the skin model.

Ianus Bifrons: The Two Faces of Metformin.

The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open?

Comparison of In Vitro Bacterial Susceptibility to Common and Novel Equine Wound Care Dressings.

Antimicrobial resistance is becoming a problem of concern in the veterinary field, necessitating the use of effective topical treatments to aid the healing of wounds. Honey has been used for thousands of years for its medicinal properties, but in recent years medical-grade Manuka honey has been used to treat infected wounds. The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The pathogens studied include ATCC lab-acclimated Pseudomonas aeruginosa, Escherichia coli, and methicillin-resistant Staphylococcus aureus and one from an equine sample submitted to the Colorado State Veterinary Diagnostic Laboratory (Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus)). An additional goal of the study was to describe the comparison of bactericidal activity of medical-grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings (20% hypertonic saline, silver sulfadiazine cream, PHMB gauze, and PHMB foam). The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting the growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka honey and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab-acclimated. Additional research for in vivo applications needs to be done to see whether differences exist in effective wound management.

Biocidal Efficacies of Contact Lens Disinfecting Solutions Against International Organization for Standardization (ISO) Compendial Organisms.

Purpose: This study was conducted to evaluate and compare the in vitro disinfection efficacies of six commercial lens cleaning and disinfecting products for planned replacement soft contact lenses. Methods: Disinfection efficacies of five multi-purpose solutions (MPSs) and one hydrogen peroxide solution (HPS) as control were evaluated in the presence of organic soil according to the International Organization for Standardization (ISO, Geneva, Switzerland) ISO 14729 stand-alone test protocol. The five specified compendial organisms, three bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens) and two fungi (Candida albicans and Fusarium solani) were incubated with each solution under standard conditions, after which microbes were recovered and quantified. Results: Each of the solutions evaluated met or exceeded the standard's primary criteria (3-log reduction of bacteria and 1-log reduction of fungi) after incubation for the manufacturer-recommended soaking time, except for COMPLETE MPS, which achieved only 0.4 ± 0.1 average log reduction for C. albicans. However, differences in efficacy between the solutions were noted. Average log reduction across all microbes for Biotrue Hydration Plus (4.6 ± 0.1) was comparable to that for CLEAR CARE PLUS HPS (4.3 ± 0.1) and greater than those for OPTI-FREE puremoist (3.6 ± 0.1), OPTI-FREE Replenish (4.0 ± 0.2), ACUVUE RevitaLens (3.9 ± 0.03), and COMPLETE MPS (3.6 ± 0.1). Biotrue Hydration Plus was especially effective at reducing the population of C. albicans (4.2 ± 0.7-log reduction). Conclusion: Products marketed for planned replacement soft CL disinfection generally meet the ISO 14729 standard's primary criteria for reducing populations of compendial organisms, with larger differences between solutions noted with C. albicans.

Antiviral and Antibacterial 3D-Printed Products Functionalised with Poly(hexamethylene biguanide).

Infection prevention and public health are a vital concern worldwide, especially during pandemics such as COVID-19 and seasonal influenza. Frequent manual disinfection and use of chemical spray coatings at public facilities are the typical measures taken to protect people from coronaviruses and other pathogens. However, limitations of human resources and coating durability, as well as the safety of disinfectants used are the major concerns in society during a pandemic. Non-leachable antimicrobial agent poly(hexamethylene biguanide) (PHMB) was mixed into photocurable liquid resins to produce novel and tailor-made covers for public facilities via digital light processing, which is a popular 3D printing technique for satisfactory printing resolution. Potent efficacies of the 3D-printed plastics were achieved in standard antibacterial assessments against S. aureus, E. coli and K. pneumoniae. A total of 99.9% of Human coronavirus 229E was killed after being in contact with the 3D-printed samples (containing the promising PHMB formulation) for two hours. In an eight-week field test in Hong Kong Wetland Park, antibacterial performances of the specially designed 3D-printed covers analysed by environmental swabbing were also found to be satisfactory. With these remarkable outcomes, antimicrobial products prepared by digital light processing 3D printing can be regarded as a reliable solution to long-term infection prevention and control.

Multifunctional Effects of Biguanide Derivative in the Application of Highly Efficient Tin-Lead Perovskite Solar Cells.

Tin-lead (Sn-Pb) mixed perovskites is beneficial to a single-junction or all-perovskite tandem device. However, the poor quality of the perovskite surface resulting from Sn2+ oxidation and uncontrollable crystallization degrades device performance and stability. Herein, based on interface engineering, a novel biguanide derivative of PZBGACl is employed that integrates different types of N-related groups to reconstruct the surface/grain boundaries of Sn-Pb perovskite. Combined with the microcorrosion effect of isopropanol solvent, PZBGACl can induce surface recrystallization of perovskite, and passivate various types of defects via hydrogen bond or Lewis acid-base interaction, leading to an excellent perovskite film with reduced stress, larger grain size, and more n-type surface. As a result, the obtained Sn-Pb solar cell achieves a power conversion efficiency of 22.0%, and exhibits excellent N2 storage/operation stability.

A Series of Biguanide Ligands and Their Cu(II) Complexes: Cholinesterase Inhibitory and Antimicrobial Properties.

In this work, a series of biguanide hydrochloride salts and their Cu(II) complexes were synthesized and screened for their acetyl/butyryl choline esterase inhibitory and antimicrobial properties. The structures of the synthesized compounds were characterised by common spectroscopic and analytical methods. Biguanide compounds showed considerably lower inhibitory activity compared to the reference drugs donepezil and galantamine. On the other hand, complexation of the biguanide compounds with Cu(II) resulted in dramatic increase in the inhibitory activity. The Cu(II) complexes showed AChE inhibitory activity with the IC50 values of 21.29±0.95-82.53±0.20 µM and those values are comparable to that of donepezil (IC50 : 18.54±1.03 µM). The synthesised compounds were also screened for their antimicrobial activity towards gram positive (+) and gram negative (-) bacteria. Compounds (12.50 mg/mL) showed important antibacterial properties with inhibition zones of 8-28 mm diameter against gram-positive and gram-negative microorganisms. Compounds A03 and A08 exhibited more antimicrobial properties towards E. coli than standard antibiotics amikacin and gentamicin.

Biguanide chitosan microneedles with cell-free DNA scavenging ability for psoriasis therapy.

High levels of cell-free DNA (cfDNA) induce psoriasis. Currently, the treatment of psoriasis has the disadvantages of penetration difficulty, suppression of normal immunity, and skin irritation. In this study, biguanide chitosan microneedles (BGC-MNs) were prepared to treat psoriasis by removing cfDNA from the dermis through the skin barrier. The effects of chitosan with different bisguanidine contents on DNA-binding capacity, biocompatibility, and inflammation inhibition were compared, revealing that chitosan containing 20% bisguanidine (BGC2) was found to have the best overall performance. In vitro, BGC2 effectively cleared cfDNA and inhibited the production of inflammatory factors. BGC-MN made from BGC2 had good mechanical and solubility properties. In vivo, BGC-MNs cleared cfDNA, reduced the level of inflammatory factors in the dermis, and exerted a good therapeutic effect on mice with psoriasis. These results suggested that BGC-MNs provided a new approach to treating psoriasis in terms of scavenging cfDNA and exerting anti-inflammatory effects.

Polyhexamethylene biguanide promotes adaptive cross-resistance to gentamicin in Escherichia coli biofilms.

Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms -a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice.

Preparation and Antimicrobial Activity of a Film-Forming Polyhexamethylene Biguanide Teat Disinfectant.

Bovine mastitis caused by infectious pathogens can lead to a decline in production performance and an increase in elimination rate, resulting in huge losses to the dairy industry. This study aims to prepare a novel dairy cow teat disinfectant with polyhexamethylene biguanide (PHMB) as the main bactericidal component and to evaluate its bactericidal activity in vitro and its disinfection effect in dairy cow teats. PHMB disinfectant with a concentration of 3 g/L was prepared with PVA-1788, propylene glycol and glycerol as excipients. When the dilution ratio is 1:4800 and the action time is 5 min, the PHMB teat disinfectant can reduce the four types of bacteria (S. agalactiae ATCC 12386, S. dysgalactiae ATCC 35666, S. aureus ATCC 6538, and E. coli ATCC 8099) by 99.99%. PHMB teat disinfectant applied on the skin of rabbits with four bacteria types achieved an average log10 reduction greater than 4. After 30 s of PHMB teat disinfectant dipping, the bacteria of cow teats were counted prior to disinfection. The mean log10 reduction in bacteria on the skin surface of 12 cows ranged from 0.99 to 3.52 after applying the PHMB teat disinfectant for 10 min. After 12 h, the PHMB teat disinfectant achieved an average log10 reduction in bacteria from 0.27 to 0.68 (compared with that prior to disinfection). These results suggested that PHMB teat disinfection has the potential to prevent and treat mastitis-causing bacteria in dairy herds.