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Antibacterial efficacy of poly(hexamethylene biguanide) immobilized on chitosan/dye-modified nanofiber membranes

Xu FX, Ooi CW, Liu BL, Song CP, Chiu CY, Wang CY, et al.

Int J Biol Macromol, 2021 Jun 30;181:508-520.
PMID: 33775766 DOI: 10.1016/j.ijbiomac.2021.03.151

This study aimed to develop a novel electrospun polyacrylonitrile (PAN) nanofiber membrane with the enhanced antibacterial property. The PAN nanofiber membrane was first subjected to alkaline hydrolysis treatment, and the treated membrane was subsequently grafted with chitosan (CS) to obtain a CS-modified nanofiber membrane (P-COOH-CS). The modified membrane was then coupled with different dye molecules to form P-COOH-CS-Dye membranes. Lastly, poly(hexamethylene biguanide) hydrochloride (PHMB) was immobilized on the modified membrane to produce P-COOH-CS-Dye-PHMB. Physical characterization studies were conducted on all the synthesized nanofiber membranes. The antibacterial efficacies of nanofiber membranes prepared under different synthesis conditions were evaluated systematically. Under the optimum synthesis conditions, P-COOH-CS-Dye-PHMB was highly effective in disinfecting a high concentration of Escherichia coli, with an antibacterial efficacy of approximately 100%. Additionally, the P-COOH-CS-Dye-PHMB exhibited an outstanding wash durability as its antibacterial efficacy was only reduced in the range of 5%-7% even after 5 repeated cycles of treatment. Overall, the experimental results of this study suggested that the P-COOH-CS-Dye-PHMB is a promising antibacterial nanofiber membrane that can be adopted in the food, pharmaceutical, and textile industries.

Matched MeSH terms: Biguanides/chemical synthesis; Biguanides/pharmacology*; Biguanides/chemistry
Electrochemically Modulated Liquid-Liquid Extraction for Sample Enrichment

Jajuli MN, Hussin MH, Saad B, Rahim AA, Hébrant M, Herzog G

Anal Chem, 2019 06 04;91(11):7466-7473.
PMID: 31050400 DOI: 10.1021/acs.analchem.9b01674

A new sample preparation method is proposed for the extraction of pharmaceutical compounds (Metformin, Phenyl biguanide, and Phenformin) of varied hydrophilicity, dissolved in an aqueous sample. When in contact with an organic phase, an interfacial potential is imposed by the presence of an ion, tetramethylammonium (TMA+), common to each phase. The interfacial potential difference drives the transfer of ionic analytes across the interface and allows it to reach up to nearly 100% extraction efficiency and a 60-fold enrichment factor in optimized extraction conditions as determined by HPLC analysis.

Matched MeSH terms: Biguanides/isolation & purification*; Biguanides/chemistry
Salting-out assisted liquid-liquid extraction coupled with hydrophilic interaction chromatography for the determination of biguanides in biological and environmental samples

Alshishani A, Salhimi SM, Saad B

J Chromatogr B Analyt Technol Biomed Life Sci, 2018 Jan 15;1073:51-59.
PMID: 29241085 DOI: 10.1016/j.jchromb.2017.12.013

A new salting-out assisted liquid-liquid extraction (SALLE) sample preparation method for the determination of the polar anti-diabetic biguanide drugs (metformin, buformin and phenformin) in blood plasma, urine and lake water samples were developed. The SALLE was performed by mixing samples (plasma (0.2mL), urine or lake water (1.0mL)) with acetonitrile (0.4mL for plasma, 0.5mL for urine or lake water), sodium hydroxide powder was then added for the phase separation. The effects of type of salting-out reagent, type of extraction solvent, volumes of acetonitrile and sample, amount of sodium hydroxide, vortexing and centrifugation times on the extraction efficiency were investigated. The upper layer, containing the biguanides, was directly injected into a HPLC unit using ZIC-HILIC column (150mm×2.1mm×3.5μm) and was detected at 236nm. The method was validated and calibration curves were linear with r2>0.99 over the range of 20-2000μgL-1for plasma and 5-2000μgL-1for urine and lake water samples. The limits of detection were in the range (3.8-5.6)μgL-1, (0.8-1.5)μgL-1and (0.3-0.8)μgL-1for plasma, urine and lake water, respectively. The accuracies in the three matrices were within 87.3-103%, 87.4-109%, 82.2-109% of the nominal concentration for metformin, buformin and phenformin, respectively. The relative standard deviation for inter- and intra -day precision were in the range of 1.0-17% for all analytes in the three matrices.

Matched MeSH terms: Biguanides/analysis*; Biguanides/isolation & purification*; Biguanides/urine; Biguanides/chemistry
Fulltext The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

Chindera K, Mahato M, Kumar Sharma A, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, et al.

Sci Rep, 2016;6:23121.
PMID: 26996206 DOI: 10.1038/srep23121

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.

Matched MeSH terms: Biguanides
Bactericidal effects of polyhexamethylene biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300

Kamaruzzaman NF, Firdessa R, Good L

J Antimicrob Chemother, 2016 May;71(5):1252-9.
PMID: 26825118 DOI: 10.1093/jac/dkv474

The treatment of skin infections caused by Staphylococcus aureus is limited by acquired antibiotic resistance and poor drug delivery into pathogen and host cells. Here, we investigated the antibacterial activities of six topically used antimicrobials and a cationic polymer, polyhexamethylene biguanide (PHMB), against intracellular MSSA strain RN4420 and MRSA strains EMRSA-15 and USA 300.

Matched MeSH terms: Biguanides
Fulltext Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies

N Amirrah I, Mohd Razip Wee MF, Tabata Y, Bt Hj Idrus R, Nordin A, Fauzi MB

Polymers (Basel), 2020 Sep 22;12(9).
PMID: 32972012 DOI: 10.3390/polym12092168

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

Matched MeSH terms: Biguanides
Fulltext Polyhexamethylene Biguanide and Nadifloxacin Self-Assembled Nanoparticles: Antimicrobial Effects against Intracellular Methicillin-Resistant Staphylococcus aureus

Kamaruzzaman NF, Pina MF, Chivu A, Good L

Polymers (Basel), 2018 May 12;10(5).
PMID: 30966555 DOI: 10.3390/polym10050521

The treatment of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge, partly due to localization of the bacteria inside the host's cells, where antimicrobial penetration and efficacy is limited. We formulated the cationic polymer polyhexamethylene biguanide (PHMB) with the topical antibiotic nadifloxacin and tested the activities against intracellular MRSA in infected keratinocytes. The PHMB/nadifloxacin nanoparticles displayed a size of 291.3 ± 89.6 nm, polydispersity index of 0.35 ± 0.04, zeta potential of +20.2 ± 4.8 mV, and drug encapsulation efficiency of 58.25 ± 3.4%. The nanoparticles killed intracellular MRSA, and relative to free polymer or drugs used separately or together, the nanoparticles displayed reduced toxicity and improved host cell recovery. Together, these findings show that PHMB/nadifloxacin nanoparticles are effective against intracellular bacteria and could be further developed for the treatment of skin and soft tissue infections.

Matched MeSH terms: Biguanides
Fulltext Sensitivity of Acanthamoeba cyst to antimicrobial agents

Noradilah, S. A., Mohamed Kamel, A. G., Anisah, N., Noraina, A. R., Yusof, S.

Malaysian Journal of Medicine and Health Sciences, 2010;6(1):111-117.
MyJurnal

Introduction: Acanthamoeba is an ubiquitous free-living protozoa which causes serious ocular problems. Acanthamoeba keratitis is becoming more prevalent amongst contact lens wearers. The disease can cause loss of vision and blindness if not treated properly. The objective of this research is to study the sensitivity of six Acanthamoeba spp. isolates, of which three were from the clinical isolates (HKL 95, HTH 40 and HS 6) and the remaining three from environmental isolates (TTT 9, TL 3 and SMAL 8) to antimicrobial agents. Methods: The antimicrobial agents chosen for this purpose were polyhexamethylene biguanide (PHMB) and chlorhexidine. Serial dilutions were perfomed for polyhexamethylene biguanide and chlorhexidine. Cyst suspensions from the chosen isolates were exposed to PHMB and chlorhexidine respectively. After 48 hours incubation time at 30°C, each mixture was filtered and filtration membrane was put onto non-nutrient agar laid with Escherichia coli. The agar plates were incubated for three days at 30°C and examined daily until day 14 to detect the presence of Acanthamoeba trophozoites under the inverted microscope. The presence of trophozoites indicated the ineffectiveness of the antimicrobial agents. Results: Both of the antimicrobial agents tested were found to be effective against Acanthamoeba cysts from all the test strains. Polyhexamethylene biguanide gave a minimum cysticidal concentration (MCC) mean value of 2.848 μg/mL while chlorhexidine showed
MCC mean value at a concentration of 3.988 μg/mL. Conlusion: It can be concluded that the Acanthamoeba cysts were sensitive to polyhexamethylene biguanide and chlorhexidine.

Matched MeSH terms: Biguanides
Evaluation of the Antibacterial Efficiency of a Combination of 1% Alexidine and Sodium Hypochlorite on Enterococcus faecalis Biofilm Models: An In Vitro Study

Thomas AR, Mani R, Reddy TV, Ravichandran A, Sivakumar M, Krishnakumar S

J Contemp Dent Pract, 2019 Sep 01;20(9):1090-1094.
PMID: 31797835

AIM: The aim of the study was to assess the antibacterial efficiency of a combination of 1% alexidine (ALX) and 5.25% sodium hypochlorite (NaOCl) against E. faecalis biofilm using a confocal scanning electron microscopy.
MATERIALS AND METHODS: An estimated 120 human root dentin disks were prepared, sterilized, and inoculated with E. faecalis strain (ATCC 29212) to develop a 3-weeks-old biofilm. The dentin discs were exposed to group I-control group: 5.25% sodium hypochlorite (NaOCl) (n = 20); group II-1% ALX + 5.25% NaOCl (n = 40); group III-1% alexidine (ALX) (n = 40) (Sigma-Aldrich, Mumbai, India); group IV-negative control: saline (n = 20). After exposure, the dentin disks were stained with the fluorescent live/dead dye and evaluated with a confocal scanning electron microscope to calculate the proportion of dead cells. Statistical analysis was done using the Kruskal-Wallis and Mann-Whitney U test (p < 0.05).
RESULTS: The maximum proportion of dead cells were seen in the groups treated with the combination of 1% ALX + 5.25% NaOCl (94.89%) and in the control group 5.25% NaOCl (93.14%). The proportion of dead cells presented in the 1% ALX group (51.79%) and negative control group saline (15.10%) were comparatively less.
CONCLUSION: The antibacterial efficiency of a combination of 1% ALX and 5.25% NaOCl was more effective when compared with 1% ALX alone.
CLINICAL SIGNIFICANCE: Alexidine at 1% could be used as an alternative endodontic irrigant to chlorhexidine, as alexidine does not form any toxic precipitates with sodium hypochlorite. The disinfection regimen comprising a combination of 1% ALX and 5.25% NaOCl is effective in eliminating E. faecalis biofilms.

Matched MeSH terms: Biguanides
Antibacterial efficacy of chitosan- and poly(hexamethylene biguanide)-immobilized nanofiber membrane

Ng IS, Ooi CW, Liu BL, Peng CT, Chiu CY, Chang YK

Int J Biol Macromol, 2020 Jul 01;154:844-854.
PMID: 32194127 DOI: 10.1016/j.ijbiomac.2020.03.127

In this study, polyacrylonitrile (PAN) nanofiber membrane was prepared by an electrospinning technique. After alkaline hydrolysis, the ion-exchange nanofiber membrane (P-COOH) was grafted with chitosan molecules to form a chitosan-modified nanofiber membrane (P-COOH-CS). Poly(hexamethylene biguanide) (PHMB) was then covalently immobilized on P-COOH and P-COOH-CS to form P-COOH-PHMB and P-COOH-CS-PHMB, respectively. The nanofiber membranes were subjected to various surface analyses as well as to the evaluations of antibacterial activity against Escherichia coli. The optimal modification conditions for P-COOH-CS-PHMB were attained by water-soluble chitosan at 50 kDa of molecular weight, coupling pH at 7, and 0.05% (w/w) of PHMB. Within 10 min of treatment, the antibacterial rate was close to 100%. Under the similar conditions of antibacterial treatment, the P-COOH-CS-PHMB exhibited a better antibacterial efficacy than the P-COOH-PHMB. When the number of bacterial cells was increased by 2000 folds, both types of nanofiber membranes still maintained the antibacterial rate close to 100%. After five cycles of repeated antibacterial treatment, the antibacterial efficacy of P-COOH-PHMB was 96%, which was higher than that of P-COOH-CS-PHMB (83%). The experimental results revealed that the PHMB-modified nanofiber membranes can be suitably applied in water treatment such as water disinfection and biofouling control.

Matched MeSH terms: Biguanides
Fulltext Comparison of the Antibacterial Efficacy of Alexidine and Chlorhexidine Against Enterococcus Faecalis: An in Vitro Study

Varadan P, Ganesh A, Konindala R, Nagendrababu V, Ashok R, Deivanayagam K

Cureus, 2017 Oct 26;9(10):e1805.
PMID: 29308333 DOI: 10.7759/cureus.1805

Introduction Root canal irrigants play an important role in reducing intracanal microorganisms, which in turn helps in achieving a successful outcome for the root canal treatment. Objective To compare the antibacterial efficacy of alexidine and chlorhexidine against Enterococcus faecalis. Methods A total of 50 extracted single-rooted teeth were randomly divided into five groups after being infected with Enterococcus faecalis. The groups were based on irrigants used: Group I - 0.4% alexidine; Group II - 1% alexidine; Group III - 1.5% percent alexidine; Group IV - 2% alexidine; Group V - 2% chlorhexidine. Following irrigation, colony-forming units were determined from the dentinal shavings collected at 400 µm depth. Results Use of 2% alexidine reduced the bacteria effectively when compared to 0.4%, 1%, and 1.5% alexidine. A statistically significant difference was not observed between 2% alexidine and 2% chlorhexidine. Discussion Alexidine, due to its higher virulence factors for bacteria and better bacterial penetrability at 400 µm depth of dentin showed better eradication of Enterococcus faecalis in comparison to chlorhexidine. Conclusion The use of 2% alexidine against Enterococcus faecalis at 400 µm depth of dentin has efficacy comparable to chlorhexidine. Hence, alexidine can be used as an alternative irrigant for chlorhexidine during endodontic procedures.

Matched MeSH terms: Biguanides
Fulltext The Development of Drugs against Acanthamoeba Infections

Siddiqui R, Aqeel Y, Khan NA

Antimicrob Agents Chemother, 2016 11;60(11):6441-6450.
PMID: 27600042 DOI: 10.1128/AAC.00686-16

For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.

Matched MeSH terms: Biguanides/pharmacology
Fulltext Antimicrobial gauze as a dressing reduces pin site infection: a randomized controlled trial

Lee CK, Chua YP, Saw A

Clin Orthop Relat Res, 2012 Feb;470(2):610-5.
PMID: 21842299 DOI: 10.1007/s11999-011-1990-z

Pin site infection is a common problem in external fixation. Plain gauze wetted with normal saline is commonly used for a pin site dressing owing to the simplicity and low cost. Evidence to support adding an antimicrobial agent in the dressing material is lacking.

Matched MeSH terms: Biguanides/administration & dosage*
Fulltext Body composition in the pathogenesis and management of diabetes: a Malaysian perspective

Osman A, Khalid BA

Asia Pac J Clin Nutr, 1994 Mar;3(1):33-9.
PMID: 24351204

There is an increasing prevalence of diabetes mellitus around the world associated with rapid sociocultural development and changing lifestyles. Increased prevalence of obesity, with a higher consumption of animal products and lower consumption of fruits and vegetables, increases the risk of diabetes mellitus and other chronic degenerative diseases. Insulin-dependent diabetes (IDD) is caused by insulin deficiency, whereas the main feature of non-insulin-dependent diabetes (NIDD) which accounts for more than 90% of diabetics, is hyperinsulinemia and insulin resistance, which may eventually lead to actual insulin deficiency. Hyperinsulinemia is undesirable because it increases the risk of developing vascular disease. In Malaysia, the prevalence of NIDD in some communities now exceeds 5%, and of impaired glucose tolerance 10%. Along with these increases in prevalence of hyperglycemia are increases in prevalence of overweight (BMI>25) and almost certainly abdominal fatness. In terms of management, nutrition is given priority. Insulin and hypoglycemic drugs (sulphonylureas or biguanides), where required, may adversely affect body composition if overused. Newer therapeutic strategies require greater attention to the underlying problem in NIDD of abdominal fatness by attention to the relevant nutritional factors, physical activity and other lifestyle factors like cigarette smoking and alcohol. The greater impact of obesity and diabetes on Malaysian women as opposed to men also needs to be addressed.

Matched MeSH terms: Biguanides
Management of patients with type 2 diabetes mellitus in MPH hospitals and health centres

Haliza, A.M., Roslan Johari, M.G., Badrulnizam, M., Rosidah, S.S., Teng, S.C., Saiful Safuan, M.S., et al.

Journal of Health Management, 2008;4(1):73-87.
MyJurnal

Diabetes mellitus is a chronic disorder with many vascular complications, leading to significant morbidity and mortality. The prevalence of Type 2 diabetes mellitus in Malaysia has risen dramatically from 6.3% (NHMS 1 in 1986); to 8.3% (NHMS 2 in 1996); and to 14.9% (NHMS 3 in 2006). An audit was conducted on patient's medical records from selected MOH health facilities to assess the control of diabetes using HbA1c. The response rate was 69.6% and the control of diabetes was poor. Only 18.4% of patients with valid HbA1c had value less than 6.5%. This is notably worst amongst patients from younger age groups. Many recommended investigations such as fundoscopy and urine microalbumin had not been done regularly. Efforts to look for various vascular complications were under-reported. About 45% of patients had been treated with 2 oral antidiabetic agents; mainly the sulphonylureas and the biguanides. Only 13.3% of patients were on insulin despite having poorly controlled disease. There is an urgent need to improve the management of diabetes mellitus in these areas:- (i) improving the glycemic control status (particularly among younger diabetic patients) with early and optimal use of oral diabetic drugs and insulin; (ii) stringent monitoring of glycemic control with adequate funds for regular performance of HbA1c (at least every 6 monthly for all diabetic patients) (iii) organizing regular updates or interactive programme for diabetes healthcare providers from primary, secondary and tertiary care; (iv) ensuring regular and prompt review of diabetic complications so that the complications can be dealt with early; (v) producing more diabetes educators to strengthen and standardize the diabetes education programme; and promote patients adherence to non-pharmacological and pharmacological interventions.

Matched MeSH terms: Biguanides
Fulltext Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii

Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.

Antibiotics (Basel), 2020 May 25;9(5).
PMID: 32466210 DOI: 10.3390/antibiotics9050276

The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.

Matched MeSH terms: Biguanides
Evaluation of the efficacy of antibacterial medical gloves in the ICU setting

Kahar Bador M, Rai V, Yusof MY, Kwong WK, Assadian O

J Hosp Infect, 2015 Jul;90(3):248-52.
PMID: 25982193 DOI: 10.1016/j.jhin.2015.03.009

Inappropriate use of medical gloves may support microbial transmission. New strategies could increase the safety of medical gloves without the risk of patient and surface contamination.

Matched MeSH terms: Biguanides

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