Treatment Of Local Infections Research Articles

Antibacterial Properties of Synthetic Cationic Bacteriochlorin Derivatives as Photosensitizers

Antibacterial photodynamic therapy (APDT) is a promising method of treatment of local infections, based on photochemical reaction of photosensitizer (PS) under irradiation with visible or near infra-red light of appropriate wavelength. A molecule of PS is activated by light energy and as a result singlet oxygen and other reactive oxygen species, which are toxic for microbes, are generated. Antibacterial action of new PS (synthetic polycationic bacteriochlorin derivatives with spectral maximum of absorbance at 760 nm) with improved features was investigated in vitro in this work. Tetra- and octacationic bacteriochlorins with lower molecular mass, as compared with ones previously proposed, turned out to be highly effective against Pseudomonas aeruginosa and Staphylococcus aureus in plankton and biofilm state: reduction of viable bacteria in biofilms reached 5log10. The dependence of the effect on PS concentration, the time of incubation with PS and light dose was ascertained. Light microscopy of biofilms after photodynamic treatment and Live/Dead staining confirmed the death of bacteria or damage of their membranes after exposure to PS and irradiation.

Effects of antimicrobial photodynamic therapy on antibiotic-resistant Escherichia coli.

This study used Electron Cryo-tomography (ECT) and fluorescent images to evaluate antimicrobial photodynamic therapy (aPDT) on the envelope architecture of a Gram-negative bacteria and the effects of combined therapy of aPDT and antibiotics. Standard and clinical suspension of Escherichia coli were submitted to photodynamic treatment with methylene blue solution (100μM) and a 100 mW LED emitting at 660 nm with 3 and 18 J of energy. As a control group, a suspension of E. coli was submitted to penicillin V for 60 min at 30 °C, to compare the damage in cell wall structure. After treatment, ECT images were collected and E. coli biofilms were grown in glass-cover slides and stained with live/dead staining for fluorescence analysis before and after treatments. Bacteria were also submitted to disc diffusion and MIC50 tests with Ampicillin, Amoxicillin + Clavulanic acid, Clindamycin and Erythromycin. For in vivo experiment Galleria mellonella larvae were infected with E. coli and treated with antibiotics, aPDT or combined therapy. ECT images presented damage to cell walls and vesicles structures inside and outside the bacteria and fluorescent images showed dose dependent effect of aPDT. Antibiotic or aPDT alone did not improve the survival of caterpillars, but the combined therapy significantly increased survival curve. ECT and fluorescent images shows that aPDT seems to promote micro-damages to cell envelope and causes the production of membrane vesicles permeabilizing cell membranes. The results showed that pre-treating bacterial cells with a photosensitizer and light make them more susceptible to antibiotics and could be an alternative to local infection treatment by resistant bacteria.

Gentamicin encapsulated within a biopolymer for the treatment of Staphylococcus aureus and Escherichia coli infected skin ulcers

Skin wound infection requires carefully long-term treatment with an immense financial burden to healthcare systems worldwide. Various strategies such as drug delivery systems using polymer matrix from natural source have been used to enhance wound healing. Natural rubber latex (NRL) from Hevea brasiliensis has shown angiogenic and tissue repair properties. Gentamicin sulfate (GS) is a broad-spectrum antibiotic which inhibits the growth of a wide variety of microorganisms and, because of this, it has also been applied topically for treatment of local infections. The aim of this study was to develop a GS release system using NRL as matrix for Staphylococcus aureus and Escherichia coli infected skin ulcers treatment, without changing drug antibiotic properties. The matrix did not change the GS antimicrobial activity against S. aureus and E. coli strains. Moreover, the NRL-GS biomembrane did not exhibit hemolytic activity, being non-toxic to red blood cells. The eluates of NRL-GS biomembranes and GS solutions did not significantly reduce the survival of Caenorhabditis elegans worms for 24 h at any of the tested concentrations. Thus, these results emphasize that the NRL-GS biomembrane proved to be a promising biomaterial for future studies on the development of dressings for topical uses, inexpensive and practicable, keeping drug antibiotic properties against pathogens and to reduce the side effects.

Antimicrobial Properties of Nonantibiotic Agents for Effective Treatment of Localized Wound Infections: A Minireview.

Wounds present serious health problems in humans and animals. Importantly, if left untreated, wounds invariably lead to long-term morbidity. The inappropriate use and costs of antibiotics place significant challenges globally and affect the health budgets of many countries. Though some antibiotics are administered systemically, treatment of localized infections, in particular, chronic wound infections, does not need such therapy-this would minimize development of antibiotic resistance. Of these measures, nanoparticles of silver, ZnO, and gold seem to give promising results against common wound pathogens while having few limitations. Chemical components of essential oils, which are extracted from different plants, have been shown to act against common wound pathogens. Plant extracts have shown different mechanisms in biofilm elimination. Chlorhexidine and chlorine derivatives act as wound antiseptics. Attempts with biological agents such as maggots have also been shown to provide anti-infective as well as mechanical removal of wound debris. Honey, including those obtained from bees, has a wide coverage against wound pathogens. Glycerin and hypertonic saline are anti-infective through the concentration-dependent killing of pathogens. Hyperbaric oxygen acts against many wound pathogens, in particular anaerobes. This review is focused on nonantibiotic attempts for the cure of localized infections, in particular, chronic wounds with common wound pathogens.

A Combinative Assembly Strategy Inspired Reversibly Borate-Bridged Polymeric Micelles for Lesion-Specific Rapid Release of Anti-Coccidial Drugs

HighlightsA combined assembly strategy from hydrophobicity-driving and reversible borate bridges is proposed for high drug-loading efficiency and superior stability.Intestinal environment-triggered drug delivery system represents an effective treatment for local infection due to the site-specific targeting and shuttling of drugs.The reduced dosage brought by the drug-loading micelles could solve the problem of drug residue in breeding industry.Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs. Herein, chitosan conjugates (SPCS) installed with sialic acid (SA) and phenylboronic acid (PBA) were synthesized, of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA. The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges. The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract. After reaching the lesions, the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release, while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside. The drug-micelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation. The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable, safe and flexible anti-infectious drug delivery systems.

Preparation and evaluation of an oral mucoadhesive gel containing nystatin-loaded alginate microparticles

Abstract Nystatin is an antifungal agent used for prophylaxis and treatment of candidiasis, especially oral mycosis. Efficacy of nystatin conventional dosage forms is limited by the short residence time and bitter taste of the drug. This research aims at designing an optimized formulation of oral mucoadhesive gel of nystatin-loaded alginate microparticles, which can be retained in the mouth. Sodium alginate solution containing nystatin was added to the solution of calcium chloride under stirring. Microparticles containing nystatin were incorporated into the Carbopol gel. Size, loading, and release profile and mucoadhesion were investigated. The most suitable microparticles with particle size of < 250 μm were prepared with alginate concentration of 1%(w/v), calcium chloride of 1%(w/v), drug:polymer concentration 1%, and ratio of alginate solution:calcium chloride of 1:10. This formulation showed 49.1% drug loading and 98.2% encapsulation efficiency. Carbopol 934 gel provided optimal mucoadhesive properties. Release profile proved a burst release, which can be attributed to the surface associated drug, followed by a slower sustained release phase for all microparticles. The developed system with ability to adhere to the oral mucosa has great appeal for treatment of localized infections and can mask bitter taste of the drug and be retained in the mouth for long periods.

Clinical analysis of 61 cases of deep neck infection

Objective: To explore the clinical experience in care for deep neck infection (DNI) and to analyze the factors influencing surgical treatment outcome. Methods: A retrospective analysis was conducted on 61 patients with DNI admitted to the Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from March 2013 to April 2019, including 33 males and 28 females, aged from 6 months to 81 years with a median age of 49 years. Patients were divided into two groups, 31 cases with localized infection (neck abscess) in Group A and 30 cases with diffuse infection (neck necrotizing fasciitis) in Group B. Patients in two groups were compared for sex, age, hospital stay, diabetes, tracheostomy, drainage methods, mediastinal infection, and pathogenic bacteria. The influence of different drainage methods on hospital stay in Group A was analyzed. SPSS 25.0 software was used for statistical analysis. Results: Of the 61 patients, 45 patients underwent surgical incision and drainage (21 cases in Group A and 24 cases in Group B), 23 patients underwent ultrasound-guided fine needle aspiration (UG-FNA) and catheter drainage (10 cases in Group A and 13 cases in Group B), and 7 patients in Group B were treated with both drainage methods. Pathogens were cultured in 31 cases (50.82%). There were significant differences in hospital stay, drainage method and mediastinal infection (χ(2) values were 26.890, 8.687 and 6.035, respectively, P<0.05), but no significant difference was found in sex, age, diabetes, tracheotomy and pathogenic bacteria (χ(2) values were 0.157, 3.685, 2.434, 3.631 and 0.807, respectively, P>0.05) between the two groups. There was no significant difference in hospital stay between two drainage methods in patients in Group A (χ(2)=1.560, P>0.05). Conclusions: There were significant differences in hospital stay, drainage method and mediastinal infection between patients with localized infection and diffuse infection, as diffuse infection is often associated with serious complications. UG-FNA and catheter drainage is an optional method for the treatment of localized infection, with minimal invasion and no influence on hospital stay.

Clinical analysis of 61 cases of deep neck infection

Objective: To explore the clinical experience in care for deep neck infection (DNI) and to analyze the factors influencing surgical treatment outcome. Methods: A retrospective analysis was conducted on 61 patients with DNI admitted to the Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from March 2013 to April 2019, including 33 males and 28 females, aged from 6 months to 81 years with a median age of 49 years. Patients were divided into two groups, 31 cases with localized infection (neck abscess) in Group A and 30 cases with diffuse infection (neck necrotizing fasciitis) in Group B. Patients in two groups were compared for sex, age, hospital stay, diabetes, tracheostomy, drainage methods, mediastinal infection, and pathogenic bacteria. The influence of different drainage methods on hospital stay in Group A was analyzed. SPSS 25.0 software was used for statistical analysis. Results: Of the 61 patients, 45 patients underwent surgical incision and drainage (21 cases in Group A and 24 cases in Group B), 23 patients underwent ultrasound-guided fine needle aspiration (UG-FNA) and catheter drainage (10 cases in Group A and 13 cases in Group B), and 7 patients in Group B were treated with both drainage methods. Pathogens were cultured in 31 cases (50.82%). There were significant differences in hospital stay, drainage method and mediastinal infection (χ(2) values were 26.890, 8.687 and 6.035, respectively, P<0.05), but no significant difference was found in sex, age, diabetes, tracheotomy and pathogenic bacteria (χ(2) values were 0.157, 3.685, 2.434, 3.631 and 0.807, respectively, P>0.05) between the two groups. There was no significant difference in hospital stay between two drainage methods in patients in Group A (χ(2)=1.560, P>0.05). Conclusions: There were significant differences in hospital stay, drainage method and mediastinal infection between patients with localized infection and diffuse infection, as diffuse infection is often associated with serious complications. UG-FNA and catheter drainage is an optional method for the treatment of localized infection, with minimal invasion and no influence on hospital stay.

Intracranial abscesses in children at Ile-Ife, Nigeria: a case series and review of literature.

Central nervous system (CNS) infections are significant causes of morbidities and mortalities in children with some being prone to the development of abscesses which can either be within the brain parenchyma or located in extracranial structures. We aimed to describe the clinical profile and outcome of children with cranial abscesses at the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC). Consecutive cases presenting at the Children Emergency Ward of OAUTHC Ile-Ife were recruited. The pattern of presentation, predisposing factors and outcome of these children were studied. Among the 641 children admitted within a 6-month period, six were diagnosed with cranial abscess giving a hospital prevalence of 0.9%. The mean duration of symptom prior to presentation was 12.7 ± 13.4days. Five (83.3%) of the patients had intracranial abscesses which were multiple in two (33.3%) children. One patient had Pott's puffy tumour following frontal sinusitis. Surgical management was done for two (33.3%), and this was by craniotomy and evacuation. Two of the patients died with a case fatality rate of 33.3%. Though uncommon, cranial abscesses remain life threatening in children especially in resource-poor settings. Early presentation and early treatment of local infections will improve outcome.

New Nanotechnologies for the Treatment and Repair of Skin Burns Infections.

Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections.

The impact of Aggregatibacter actinomycetemcomitans biofilm-derived effectors following antimicrobial photodynamic therapy on cytokine production in human gingival fibroblasts.

Antimicrobial photodynamic therapy (aPDT) is an effective adjunctive therapeutic modality for the treatment of local infections, including periodontitis and peri-implantitis. After receiving aPDT, microbial cells in the biofilm structure may produce and/ or release soluble biofilm-derived effectors (BDEs), which may affect the biology of the host cells in the community context of their surrounding microenvironment. Given the fact that no study has investigated the role of BDEs following aPDT in the pathogenesis of infectious diseases, the aim of the current study was to determine the effect of BDEs of Aggregatibacter actinomycetemcomitans following exposure to sub-lethal doses of indocyanine green (ICG)-aPDT on human gingival fibroblasts (HGFs) in terms of cytokines produced. In this study, we evaluated the effect of biofilm-conditioned medium (BCM) resulting from the treatment of A. actinomycetemcomitans biofilm with a sub-lethal dose of aPDT on cytokines production, including IL-6, IL-8, CXCL10, TGF-β, and bFGF of HGFs using enzyme-linked immunoassays (ELISA). The sensitivity of cytokines to BDEs was determined by micro-titer plates. The maximal sub-lethal dose of ICG-PDT was 20.15 μM/mL ICG at a fluence of 31.2 J/cm2. The BCM of ICG-PDT-treated viable A. actinomycetemcomitans significantly reduced IL-6, IL-8, and CXCL10 levels compared to the BCM of untreated viable A. actinomycetemcomitans (78-, 93-, and 61.6-fold reduction, respectively; all P < 0.01). TGF-β and bFGF were strongly induced by BCM of ICG-PDT treated viable A. actinomycetemcomitans (by 57.7 and 36.1 folds, respectively; both P < 0.05). The BCM of untreated viable A. actinomycetemcomitans degraded most of the CxCL10, TGF-β and bFGF (58.8, 61.5, and 71.6%, respectively) in 24 h, while it degraded 9.3% of IL-6 and 15.1% of IL-8 after 24 h. The results of the current study revealed that a sub-lethal dose of ICG-aPDT through the effect of BCM on HGFs could not only significantly reduce the production of pro-inflammatory cytokines but also promoted their role in periodontal regeneration due to increasing the bFGF level. Altogether, ICG-aPDT, with it's antimicrobial effects reduces inflammation and induces of tissue regeneration resulting from BCM, can be considered an efficient adjunctive therapeutic method for the treatment of local infections.

Changes of microbial cell survival, metabolic activity, efflux capacity, and quorum sensing ability of Aggregatibacter actinomycetemcomitans due to antimicrobial photodynamic therapy-induced bystander effects.

The bystander effects, whereby naive (bystander) microbial cells near microbial cells directly exposed to certain treatment show responses that would not have happened in the absence of the directly targeted microbial cells, is recently documented in the field of microbiology. In this article, we discuss that substantial bystander responses are also observed after antimicrobial photodynamic therapy (aPDT) using curcumin (Cur). Bystander effects induced by whole bacterial cell suspension (WBCST), cell-free supernatants fluid (CFSFT), and bacterial cell pellet (BCPT) obtained from A. actinomycetemcomitans culture treated with Cur-aPDT on cell survival, quorum sensing (QS) ability, metabolic activity and efflux capacity of A. actinomycetemcomitans were determined using microbial viability assay, Escherichia coli-based bioassay, XTT reduction method, and ethidium bromide (EtBr) accumulation assay, respectively. A. actinomycetemcomitans cell survival reduced by 82.7% (P = 0.001) and 76.2% (P = 0.01) after exposure to WBCST and CFSFT, respectively. The A. actinomycetemcomitans population increased by 5.5% (P = 0.7) after exposure to BCPT. Bacterial metabolic activity decreased by 42.6% (P = 0.02), 35.3% (P = 0.03), and 9.4% (P = 0.5) after exposure to WBCST, CFSFT, and BCPT, respectively. A. actinomycetemcomitans exposed to WBCST, CFSFT, and BCPT showed a reduction of 83.2% (P = 0.001), 77.2% (P = 0.01) and 21.9% (P = 0.09) in the QS mediator compared to the WBCSU, CFSFU, and BCPU of untreated A. actinomycetemcomitans, respectively. No significant change of the EtBr accumulation was observed in the three preparations of the Cur-aPDT-treated culture (i.e. WBCST, CFSFT, and BCPT) compared to their respective controls. The results of the current study revealed that Cur-aPDT could significantly reduce microbial cell survival, cell metabolic activity, efflux capacity, and QS ability through the bystander effects. As a result, the bystander effects of Cur-aPDT along with the direct effect of Cur-aPDT can enhance the efficiency of aPDT as an adjunct therapeutic strategy for treatment of local infections.

Antimicrobial effect of methylene blue formulations with oxygen carrier at different pHs: preliminary study

Objective: Evaluate methylene blue (MB) formulations containing oxygen carrier at different pHs in antimicrobial photodynamic therapy (aPDT). Material and Methods: Biofilms of Pseudomonas aeruginosa PA01 formed over acrylics specimens during five days were treated with aPDT using different formulations: MB/pH 7.4; MB/pH 5.6; MB/carrier pH 7.4; MB/carrier pH 5.6. Biofilms not exposed to treatment were used as a control. Blind examiner for the experimental groups performed the counting of colonies per ml suspension (CFU/ml). Two-way ANOVA was used to determine the effect of factors solvent (carrier vs water) and pH (7.4 vs 5.6). One-way ANOVA and post-hoc Tukey’s test was used to evaluate differences among the five groups (control; MB/carrier pH 7.4; MB pH 7.4; MB/carrier pH 5.6; MB pH 5.6). The Statistics 8.0 software was used (P&lt;0.05). Results: All of photodynamic therapy groups showed significant reduction in P. aeruginosa compared to the control group. The solvent factor was not significant (P=0.18), while the pH factor presented statistical significance (P=0.01). When the carrier was used, MB formulation at pH 7.4 presented a statistically greater reduction of P. aeruginosa than the formulation with pH 5.6. Conclusion: The PDT using methylene blue formulations with oxygen carrier demonstrated potential for the treatment of localized infections by P. aeruginosa. MB formulations with oxygen carrier and pH 7.4 resulted in higher antimicrobial effect and should be considered for future studies with multispecies biofilms. KeywordsAntimicrobial photodynamic therapy; biofilm; laser; Pseudomonas aeruginosa.

Antimicrobial biomaterials in the prevention and local treatment of infection in orthopedics

Antimicrobial biomaterials in the prevention and local treatment of infection in orthopedics

Mixed-charge pseudo-zwitterionic mesoporous silica nanoparticles with low-fouling and reduced cell uptake properties

The design of drug delivery systems needs to consider biocompatibility and host body recognition for an adequate actuation. In this work, mesoporous silica nanoparticles (MSNs) surfaces were successfully modified with two silane molecules to provide mixed-charge brushes (-NH3⊕/-PO3⊝) and well evaluated in terms of surface properties, low-fouling capability and cell uptake in comparison to PEGylated MSNs. The modification process consists in the simultaneous direct-grafting of hydrolysable short chain amino (aminopropyl silanetriol, APST) and phosphonate-based (trihydroxy-silyl-propyl-methyl-phosphonate, THSPMP) silane molecules able to provide a pseudo-zwitterionic nature under physiological pH conditions. Results confirmed that both mixed-charge pseudo-zwitterionic MSNs (ZMSN) and PEG-MSN display a significant reduction of serum protein adhesion and macrophages uptake with respect to pristine MSNs. In the case of ZMSNs, this reduction is up to a 70–90% for protein adsorption and c.a. 60% for cellular uptake. This pseudo-zwitterionic modification has been focused on the aim of local treatment of bacterial infections through the synergistic effect between the inherent antimicrobial effect of mixed-charge system and the levofloxacin antibiotic release profile. These findings open promising future expectations for the effective treatment of bacterial infections through the use of mixed-charge pseudo-zwitterionic MSNs furtive to macrophages and with antimicrobial properties. Statement of SignificanceHerein a novel antimicrobial mixed-charge pseudo-zwitterionic MSNs based system with low-fouling and reduced cell uptake behavior has been developed. This chemical modification has been performed by the simultaneous grafting of short chain organosilanes, containing amino and phosphonate groups, respectively. This nanocarrier has been tested for local infection treatment through the synergy between the antimicrobial effect of mixed-charge brushes and the levofloxacin antibiotic release profile.

Bacteriocin Isolated from Lactobacillus Rhamnosus L34 Has Antibacterial Effects in a Rabbit Model of Infection After Mandible Fracture Fixation.

BackgroundRigid internal fixation (RIF) technology is a recently developed fracture fixation technique in which use of specific antibiotics before and after the operation and timely treatment of local infections is necessary.Material/MethodsThe bacteriocins were isolated from Lactobacillus rhamnosus L34. Twenty-four New Zealand White female rabbits were divided into 2 groups: bacteriocins and control group. After mandible fracture fixation, the rabbits were infected with S. aureus and subsequently injected with either bacteriocins or saline. The biofilm samples were harvested from rabbits euthanized on the 1st, 3rd, and 5th days and observed using a fluorescence microscope. Blood samples were collected at 1 h, 12 h, 1 day, 3 days, and 5 days after the injection of either bacteriocin or saline to test the level of C-reactive protein and TNF-α.ResultsSignificant differences in the biofilm formation were evident between the bacteriocins and saline treatment group on days 1, 3, and 5. Moreover, the serum levels of TNF-α and CRP after treatment with bacteriocins were significantly lower than in controls.ConclusionsUse of bacteriocins isolated from Lactobacillus rhamnosus L34 may be a promising way to control infections of mandible fracture after internal fixation in vivo.

Applications of Bacteriophages in the Treatment of Localized Infections in Humans.

In the recent years, multidrug-resistant bacteria have become a global threat, and phage therapy may to be used as an alternative to antibiotics or, at least, as a supplementary approach to treatment of some bacterial infections. Here, we describe the results of bacteriophage application in clinical practice for the treatment of localized infections in wounds, burns, and trophic ulcers, including diabetic foot ulcers. This mini-review includes data from various studies available in English, as well as serial case reports published in Russian scientific literature (with, at least, abstracts accessible in English). Since, it would be impossible to describe all historical Russian publications; we focused on publications included clear data on dosage and rout of phage administration.

In Vitro Antimicrobial Effect of Bioadhesive Oral Membrane with Chlorhexidine Gel.

This study aimed to evaluate in vitro the antimicrobial effect of a bioadhesive chitosan-based oral membrane with chlorhexidine for local treatment of infections in the oral tissues. Five oral membranes of different compositions were tested: 5% chitosan (G1); 5% chitosan ± 0.2% chlorhexidine (G2), 5% chitosan ± 0.6% chlorhexidine (G3), 5% chitosan ± 1.0% chlorhexidine (G4), and 5% chitosan ± 2.0% chlorhexidine (G5). Also, five gel types were tested according to the following compositions: 5% chitosan gel (G6), 0.2% chlorhexidine gel (G7), 2.0% chlorhexidine gel (G8), 5% chitosan gel ± 0.2% chlorhexidine gel (G9), and 5% chitosan gel ± 2.0% chlorhexidine gel (G10). The antimicrobial action of the samples was tested against Candida albicans and Streptococcus mutans through antibiogram by measuring the inhibition halos. Data were statistically analyzed by Kruskal-Wallis and one-way ANOVA followed by Tukey test (p<0.05). The 2.0% chlorhexidine membrane (G5) and the disks containing 2.0% chlorhexidine gel (G8) showed the greatest inhibition halos for both microorganisms, with statistically significant difference when compared to others tested groups (p=0.008) only for Candida albicans inhibitions results. All the other formulations of membranes and gels showed inhibition halos, but without statistically significant difference. The bioadhesive chitosan-based oral membrane with 2% chlorhexidine and 2% chlorhexidine gel were the most effective in inhibiting the tested microorganisms.

The Effect of Polymer Microstructure on Encapsulation Efficiency and Release Kinetics of Citropin 1.1 from the Poly(ε-caprolactone) Microparticles.

Cationic antimicrobial peptides represent a promising therapeutic option against multidrug-resistant bacteria for the treatment of local infections. However, due to their low stability and potential toxicity, there are limited possibilities for their application in clinical practice. In this study, different poly(ε-caprolactone) (PCL) microparticles (MPs) loaded with citropin 1.1 (CIT) were investigated in order to demonstrate the effect of the polymer microstructure on the encapsulation efficiency (EE) and kinetics of the peptide release from the newly developed devices. The characteristics of the new systems in terms of surface morphology, particle size, EE and zeta potential analysis, as well as the haemolytic activities of the peptide were investigated. The in vitro release kinetics of CIT from the MPs was also investigated. CIT loading was favoured by a high content of negative charged linear polymer chains in the PCL structure. The presence of non-charged, amorphous macrocycle domains results in faster degradation of the PCL matrix. Depending on the crystallinity of the PCL, the peptide release exhibited a near-zero-order or near-first-order profile with no “burst release”. The results indicated that CIT-loaded PCL MPs could potentially be a promising drug delivery system (DDS) for the treatment of local infections.

A Novel Delivery System for the Controlled Release~of Antimicrobial Peptides: Citropin 1.1 and Temporin A.

Antimicrobial peptides (AMPs) are prospective therapeutic options for treating multiple-strain infections. However, clinical and commercial development of AMPs has some limitations due to their limited stability, low bioavailability, and potential hemotoxicity. The purpose of this study was to develop new polymeric carriers as highly controlled release devices for amphibian peptides citropin 1.1 (CIT) and temporin A (TEMP). The release rate of the active pharmaceutical ingredients (APIs) was strongly dependent on the API characteristics and the matrix microstructure. In the current work, we investigated the effect of the polymer microstructure on in vitro release kinetics of AMPs. Non-contact laser profilometry, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) were used to determine the structural changes during matrix degradation. Moreover, geno- and cytotoxicity of the synthesized new carriers were evaluated. The in vitro release study of AMPs from the obtained non-toxic matrices shows that peptides were released with near-zero-order kinetics. The peptide “burst release” effect was not observed. New devices have reached the therapeutic concentration of AMPs within 24 h and maintained it for 28 days. Hence, our results suggest that these polymeric devices could be potentially used as therapeutic options for the treatment of local infections.