Chlorhexidine Dihydrochloride Research Articles

Dual drug release profiles of salicylate-based polymers and encapsulated chlorhexidine as potential periodontitis treatments

Salicylate-based poly(anhydride-esters; SAPAEs) have demonstrated wound healing properties due to salicylic acid (SA) release during polymer degradation. Additionally, the polymers are deformable and self-adhesive due to their low Young’s modulus, lower glass transition temperature ( Tg), and inherent tackiness at body temperature. These properties make them particularly well-suited for therapeutic use in the bacteria-laden environment of the oral cavity. To enhance their therapeutic capabilities, the antiseptic chlorhexidine dihydrochloride was physically incorporated into SAPAEs for dual release of antiseptic and anti-inflammatory upon degradation. This study analyzes the thermomechanical properties of two SAPAE compositions (adipate homopolymer and 50:50 adipate:sebacate copolymer) and the release of chlorhexidine (incorporated at 10% (w/w)) from these polymers. Polymer adhesivity was monitored as a function of chlorhexidine incorporation and in vitro degradation time. Throughout in vitro degradation, the polymer systems had a low Young’s modulus and a Tg at or near body temperature. Incorporation of the antiseptic further decreased Young’s modulus and increased both the Tg and adhesivity. The release profiles were also evaluated and determined to be similar for the homopolymer and copolymer, although the homopolymer degradation occurred over a longer time period. Overall, the SAPAE systems have favorable properties for periodontal disease treatments by virtue of their controlled degradability, deformability, adhesivity, and release profiles with encapsulated antiseptic.

In-situ forming PLGA implants: Towards less toxic solvents

In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible solvent. The drug is dissolved or dispersed in this solution. Upon contact with aqueous body fluids, the solvent diffuses into the surrounding tissue and water penetrates into the formulation. Consequently, PLGA precipitates, trapping the drug. Often, N-methyl-2-pyrrolidine (NMP) is used as a water-miscible solvent. However, parenteral administration of NMP raises toxicity concerns. The aim of this study was to identify less toxic alternative solvent systems for in-situ forming PLGA implants. Various blends of polyethylene glycol 400 (PEG 400), triethyl citrate (TEC) and ethanol were used to prepare liquid formulations containing PLGA, ibuprofen (as an anti-inflammatory drug) and/or chlorhexidine dihydrochloride (as an antiseptic agent). Implant formation and drug release kinetics were monitored upon exposure to phosphate buffer pH 6.8 at 37 °C. Furthermore, the syringeability of the liquids, antimicrobial activity of the implants, and dynamic changes in the latter’s wet mass and pH of the release medium were studied. Importantly, 85:10:5 and 60:30:10 PEG 400:TEC:ethanol blends provided good syringeability and allowed for rapid implant formation. The latter controlled ibuprofen and chlorhexidine release over several weeks and assured efficient antimicrobial activity. Interestingly, fundamental differences were observed concerning the underlying release mechanisms of the two drugs: Ibuprofen was dissolved in the solvent mixtures and partially leached out together with the solvents during implant formation, resulting in relatively pronounced burst effects. In contrast, chlorhexidine dihydrochloride was dispersed in the liquids in the form of tiny particles, which were effectively trapped by precipitating PLGA during implant formation, leading to initial lag-phases for drug release.

Efficacy of Intra-Pocket Application of Two Antimicrobial Agents as an Adjunct to Mechanotherapy of Chronic Periodontitis (a Comparative Study)

Numerous studies have been performed to evaluate the effectiveness of the use of locally delivered antimicrobials as an adjunct to mechanotherapy in treatment of chronic periodontitis. Some studies were resulted in improved clinical outcomes and others were not. The aim of this study is evaluation of the efficacy and safety of subgingival application of a (10 mg metronidazole gel), (1% chlorhexidine collagen gel) and (CHLOSITE® GHIMAS, Italy) gel which is a combination of two chlorhexidine formulations: 0.5% chlorhexidine digluconate and 1.0% chlorhexidine dihydrochloride), as an adjunct to mechanical treatment (scaling and root planing) (SRP) of chronic periodontitis. A total of 120 sites from 15 patients with age range of (24-55 years), who had periodontal pockets measuring 5-9 mm and had been diagnosed as chronic periodontitis cases, were selected for the study. The 4-quadrant split-mouth design was used in this study. The pocket sites in each patient were randomly assigned to 4 groups (30 sites for each):(Group A) GA=(SRP) only.(Group B) GB=(SRP) + 10 mg metronidazole gel.(Group C) GC=(SRP) + 1% chlorhexidine collagen gel. (Group D) GD=(SRP) + CHLOSITE®Clinical parameters including (plaque index PI), (gingival index GI), (gingival bleeding index) GBI, (probing pocket depth PPD) & (clinical attachment level CAL) were measured and recorded at baseline before any treatment at (day 0) then the treatment was performed at the same day, The clinical parameters were also recorded at (day 30) & (day 90), in the selected sites of the four groups. The results of this study obviously showed a statistically significant reduction of all clinical parameters in all groups at (day 30 & day 90) from the base line (day 0). GD=(SRP) + CHLOSITE® revealed a reduction of the clinical parameters than groups (A, B and C) and the differences were highly statistically significant.

A laboratory investigation on the effect of biguanide- and pyridine-derived antiseptics on the adhesion of resin composites to dentin.

Optimal bonding of adhesive restorations to dentin is crucial to prevent microleakage and enhance the survival of root-filled teeth. The aim of this study was to investigate the effect of chlorhexidine (CHX), alexidine (ALX) and octenidine dihydrochloride (OCT) on the bond strength of resin composites to coronal dentin. Human coronal dentin specimens were treated with 2% CHX, 0.1% ALX, 0.1% OCT or saline then restored with traditional or bulk-fill resin composites. The adhesion strength between the resin and dentin was measured using the microtensile bond strength and failure mode was determined using a stereomicroscope. Treatment with ALX and OCT resulted in significantly greater μTBS compared with CHX and saline, irrespective of the resin composite used. Alexidine treatment predominantly resulted in mixed failure, while adhesive failures were frequently observed in CHX and saline-treated dentin. In conclusion, final irrigation with ALX or OCT improved the bonding of resin composites to dentin.

Characterization and Molecular Modelling of Non-Antibiotic Nanohybrids for Wound Healing Purposes.

The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.

In-situ forming implants for dual controlled release of chlorhexidine and ibuprofen for periodontitis treatment: Microbiological and mechanical key properties

In-situ forming implants (ISFI) which simultaneously release an antimicrobial and anti-inflammatory drug in a controlled manner offer an interesting potential for local periodontitis treatment. In this study, poly(lactic-co-glycolic acid) (PLGA)-based implants loaded with chlorhexidine and ibuprofen were investigated, in particular with respect to their antimicrobial and mechanical key properties. PLGA (Resomer RG 502H) was dissolved in N-methyl pyrrolidone (NMP). Chlorhexidine dihydrochloride and ibuprofen (free acid) were added as well as acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC, Methocel, E50) as adhesion enhancer. Upon contact with aqueous fluids, the NMP diffuses out and water into the formulation, causing polymer precipitation and drug entrapment. The antimicrobial activity against periodontal pathogens was studied using the agar-well diffusion test, time-kill studies and growth curve method. The syringeability of the liquid formulations and mechanical key properties of the in-situ formed implants were investigated using a texture analyzer. A commercially available gel used for local periodontitis treatment, loaded with chlorhexidine dihydrochloride and chlorhexidine digluconate (Chlo-site) was studied for reasons of comparison. Importantly, the investigated ISFIs showed a strong and rapid antibacterial activity against all the selected pathogens, while maintaining suitable mechanical properties. The simultaneous release of ibuprofen did not reduce the desired antimicrobial effect of chlorhexidine.

The experience of using a bacteriophages-based complex antibacterial and analgesic drug in gel formulation in women who underwent various instrumental and diagnostic and treatment interventions

During the spread of bacterial infections with extensive drug resistance, the potential of existing antibacterial drugs is significantly reduced. The medical community is seeking opportunities for the rational use of antibacterial drugs, the development of new drugs, as well as the use of alternative treatments for these infections.
 Aim. The objective of this study was to evaluate the effectiveness of the use of a complex antibacterial and analgesic drug based on bacteriophages in gel form during various instrumental studies and diagnostic procedures in order to minimize the risk of the urinary system infections complications.
 Materials and methods. The study included 235 women aged 18 to 75 years who underwent treatment at the Moscow State Clinical Hospital named after Spasokukotsky and in the clinic of urology of Moscow State University of Medicine and Dentistry from September 2019 to January 2020. During the manipulation, all patients of the main group (n=120) used a developed preparation based on bacteriophages, and in the control group (n=115), a topical gel based on chlorhexidine dihydrochloride and lidocaine hydrochloride was used. All patients before the manipulation, as well as 10 days after the manipulation, underwent bacteriological analysis of urine. Efficiency assessment was carried out on the basis of laboratory data obtained, as well as according to the visual analogue scale of the pain syndrome severity.
 Results. None of the patients in the main group showed intolerance, side effects and allergic reactions of the developed drug based on bacteriophages. Bacteriological analysis of urine received before manipulation in both groups showed the absence of clinically significant titers of pathogenic bacteria, while 1 week after manipulation the number of titers of pathogenic bacteria (104) was significantly higher in the control group (p0.04). In patients of the main group, the incidence of dysuria was lower compared with the control group (p0.05).
 Conclusion. The study showed good tolerance of the developed drug and its clinical effectiveness in reducing the number of symptomatic bacteriuria; severity of pain after undergoing manipulation was relatively lower in the main group of patients. Conducting multicenter studies with the inclusion of a larger number of patients in the future will reduce the economic costs associated with treating patients by reducing the number of cases of nosocomial infections and reducing postoperative time spent by patients in the hospital.

Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus Faecium Isolates.

We investigated the suitability of a newly developed biocide susceptibility test system based on microtiter plates containing vacuum dried biocides as a fast and reliable screening method. The evaluated substances included the cationic biocides benzalkonium chloride (BAC), chlorhexidine dihydrochloride (CHX), cetylpyridinium chloride, didecyldimethylammonium chloride, and octenidine dihydrochloride. Testing a selection of Escherichia coli and enterococci, the biocide microtiter plates provided results comparable to those obtained from broth microdilution according to ISO 20776-1. Broad MIC ranges allowed for testing gram-positive and gram-negative species with the same plate design. In the second part of our study, we applied the established method to analyze the susceptibility of 90 clinical Enterococcus faecium isolates from a German university hospital, as previous studies have indicated a link between reduced susceptibility to substances such as CHX and BAC and vancomycin resistance. We therefore determined MIC and minimum bactericidal concentrations (MBC) for 48 non-clonal vancomycin susceptible and 42 non-clonal vancomycin resistant isolates, but MIC95 and MBC95 were quite similar in both groups. Our easy to handle and ready to use test system enables the routine surveillance of bacterial tolerance towards disinfectants in hospitals. As a result, hygiene measures can be adapted and nosocomial infections controlled despite increasing prevalence of antibiotic-resistant bacteria.

Essential Oil from Psidium cattleianum Sabine (Myrtaceae) Fresh Leaves: Chemical Characterization and in vitro Antibacterial Activity Against Endodontic Pathogens

Endodontic infections result from oral pathogenic bacteria which reach and infect dental pulp, as well as surrounding tissues, through cracks, unrepaired caries and failed caries restorations. This study aims to determine the chemical composition of essential oil from Psidium cattleianum leaves (PC-EO) and to assess its antibacterial activity against endodontic bacteria. Antibacterial activity of PC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by the broth microdilution method on 96-well microplates. Bacteria Porphyromonas gingivalis (MIC = 20 µg/mL), Prevotella nigrescens (MIC = 62.5 µg/mL), Fusobacterium nucleatum (MIC = 12.5 µg/mL), Actinomyces naeslundii (MIC = 50 µg/mL), Bacteroides fragilis (MIC = 12.5 µg/mL), Aggregatibacter actinomycetemcomitans (MIC = 6.25 µg/mL) and Peptostreptococcus anaerobius (MIC = 62.5 µg/mL) were evaluated and compared to chlorhexidine dihydrochloride (CDH), the positive control. PC-EO was obtained by hydrodistillation with the use of a Clevenger-type apparatus whereas its chemical composition was analyzed by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Viridiflorol (17.9%), β-caryophyllene (11.8%), 1,8-cineole (10.8%) and β-selinene (8.6%) were the major constituents found in PC-EO, which exhibited high antibacterial activity against all endodontic pathogens under investigation. Therefore, PC-EO, a promising source of bioactive compounds, may provide therapeutic solutions for the field of endodontics.

Comparative evaluation of 2% turmeric extract with nanocarrier and 1% chlorhexidine gel as an adjunct to scaling and root planing in patients with chronic periodontitis: A pilot randomized controlled clinical trial.

Context:Nanoparticles, owing to their smaller size, penetrate regions inaccessible to other delivery systems, such as periodontal pockets. Thus, the present study aimed to comparatively evaluate efficacy of 2% curcumin with nanocarrier and 1% chlorhexidine gel as a local drug delivery (LDD) in the treatment of periodontal pockets.Materials and Methods:Forty-five chronic periodontitis patients with pocket depth 5–7 mm in two or more teeth were selected. Full-mouth scaling and root planing (SRP) was done for all patients followed by random allocation to the three treatment groups, namely SRP group (Group 1), 2% curcumin with nanogel (Group 2), and 1% chlorhexidine gel (Group 3). Clinical parameter assessment and microbiological analysis of subgingival plaque samples for Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythia (Tf) was done at baseline, 21st day, and 45th day.Results:The results showed that when the two LDD agents were used as an adjunct to SRP in chronic periodontitis, there was an improvement in all clinical parameters. Evaluation of microbiological parameters also showed a significant reduction in Aa, Pg, and Tf levels. Comparison of 2% turmeric extract with a nanocarrier system with 1% chlorhexidine gel showed that both the agents had a comparable antibacterial effect on the three selected periodontopathic bacteria.Conclusion:The present study showed that both the LDD agents showed an effective improvement of clinical and microbiologic parameters. 2% curcumin delivered with a nanocarrier system showed results comparable to chlorhexidine gel and hence shows promising future as an LDD agent in the treatment of periodontal pockets.

In-situ forming implants for the treatment of periodontal diseases: Simultaneous controlled release of an antiseptic and an anti-inflammatory drug.

Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP) was used as water-miscible solvent, acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC) was added to enhance the implants' stickiness/bioadhesion upon formation within the periodontal pocket. Different drug forms exhibiting substantially different solubilities were used: chlorhexidine dihydrochloride and digluconate as well as ibuprofen free acid and lysinate. The initial drug loadings were varied from 1.5 to 16.1%. In vitro drug release, dynamic changes in the pH of the surrounding bulk fluid and in the systems' wet mass as well as polymer degradation were monitored. Importantly, the release of both drugs, chlorhexidine and ibuprofen, could effectively be controlled simultaneously during several weeks. Interestingly, the tremendous differences in the drug forms' solubilities (e.g., factor >5000) did not translate into major differences in the resulting release kinetics. In the case of ibuprofen, this can likely (at least in part) be attributed to significant drug-polymer interactions (ibuprofen acts as a plasticizer for PLGA). In the case of chlorhexidine, the release of the much less soluble dihydrochloride was even faster compared to the more soluble digluconate (when combined with ibuprofen free acid). In the case of ibuprofen, at higher initial drug loadings also limited solubility effects within the implants seem to play a role, in contrast to chlorhexidine. In the latter case, instead, increased system porosity effects likely dominate at higher drug loadings.

Effects of Ultrasound on Zinc Oxide/Vermiculite/Chlorhexidine Nanocomposite Preparation and Their Antibacterial Activity.

Microbial infection and biofilm formation are both problems associated with medical implants and devices. In recent years, hybrid organic-inorganic nanocomposites based on clay minerals have attracted significant attention due to their application potential in the field of antimicrobial materials. Organic drug/metal oxide hybrids exhibit improved antimicrobial activity, and intercalating the above materials into the interlayer of clay endows a long-term and controlled-release behavior. Since antimicrobial activity is strongly related to the structure of the material, ultrasonic treatment appears to be a suitable method for the synthesis of these materials as it can well control particle size distribution and morphology. This study aims to prepare novel, structurally stable, and highly antimicrobial nanocomposites based on zinc oxide/vermiculite/chlorhexidine. The influence of ultrasonic treatment at different time intervals and under different intercalation conditions (ultrasonic action in a breaker or in a Roset’s vessel) on the structure, morphology, and particle size of prepared hybrid nanocomposite materials was evaluated by the following methods: scanning electron microscopy, X-ray diffraction, energy dispersive X-ray fluorescence spectroscopy, carbon phase analysis, Fourier transforms infrared spectroscopy, specific surface area measurement, particle size analysis, and Zeta potential analysis. Particle size analyses confirmed that the ultrasonic method contributes to the reduction of particle size, and to their homogenization/arrangement. Further, X-ray diffraction analysis confirmed that ultrasound intercalation in a beaker helps to more efficiently intercalate chlorhexidine dihydrochloride (CH) into the vermiculite interlayer space, while a Roset’s vessel contributed to the attachment of the CH molecules to the vermiculite surface. The antibacterial activity of hybrid nanocomposite materials was investigated on Gram negative (Escherichia coli, Pseudomonas aeruginosa) and Gram positive (Staphylococcus aureus, Enterococcus faecalis) bacterial strains by finding the minimum inhibitory concentration. All hybrid nanocomposite materials prepared by ultrasound methods showed high antimicrobial activity after 30 min, with a long-lasting effect and without being affected by the concentration of the antibacterial components zinc oxide (ZnO) and CH. The benefits of the samples prepared by ultrasonic methods are the rapid onset of an antimicrobial effect and its long-term duration.

In-situ forming implants loaded with chlorhexidine and ibuprofen for periodontal treatment: Proof of concept study in vivo.

Control of infection and inflammation is crucial for the success of periodontal treatment. In this study, in-situ forming implants (ISFI) loaded with chlorhexidine dihydrochloride (CHX) and ibuprofen (IBU) were developed and tested to optimize periodontal treatment outcomes. Release profiles were promising. Exposure to 1.5% and 5.3% CHX-IBU loaded ISFI's release media decreased significantly the P. gingivalis growth up to 20-fold and 35-fold, respectively, after 48 h (p < 0.05). The metabolic activity assay of gingival epithelial cells (EC) demonstrated 1.5% CHX-IBU-loaded ISFI to be non-toxic, therefore, it was selected for further experimentation. Furthermore, significant down-regulation of TNF-α release (34% at 6 h and 43% at 24 h, p < 0.05) in P. gingivalis lipopolysaccharide (Pg-LPS) stimulated EC exposed to 1.5% CHX-IBU ISFI release medium was demonstrated by ELISA. In vivo, 1.5% CHX-IBU ISFI was injected into the periodontal pocket in an experimental periodontitis mouse model and the reduction in inflammation and improvement in periodontal wound healing was evaluated through inflammatory cell scoring and histomorphometry at 7- and 15-days post-treatment. The results indicate that CHX-IBU loaded ISFI could be efficient as adjuvant to periodontal therapy for the control of infection and inflammation. Moreover, other (e.g., pro-regenerative) drugs could be incorporated into ISFI to further improve periodontal treatment outcomes.

Hybrid Antibacterial Nanocomposites Based on the Vermiculite/Zinc Oxide-Chlorhexidine

The hybrid nanocomposite materials based on the vermiculite/zinc oxide-chlorhexidine were prepared in two steps. In the first step the vermiculite/zinc oxide nanocomposite was prepared by the mechanochemical method followed by a heat treatment at 650 °C for 90 min. In the second step the chlorhexidine dihydrochloride was intercalated to the vermiculite/zinc oxide nanocomposite in weight ratio 1:1, 1:2, 1:4, 2:1 and 4:1 (wt%) thereby vermiculite/zinc oxide-chlorhexidine nanocomposites were prepared. Phase analysis, crystal structure, phase transformation, chemical composition and particle size of the prepared hybrid nanocomposite materials were using X-ray diffraction methods, energy dispersive X-ray fluorescence spectroscopy, carbon phase analysis, Fourier transforms infrared spectroscopy and particle size analysis. Antibacterial activity of hybrid nanocomposite materials was investigated on Gram negative (E. coli, P. aeruginos.) and the Gram positive (S. aureus, E. faecalis) bacterial strain and against yeast Candida a. by finding the minimum inhibitory concentration. The hybrid nanocomposite materials exhibit high antibacterial activity after 30 minutes with a long-lasting effect persisting up to 5 days. Dependence of the zinc oxide and chlorhexidine concentration in vermiculite structure on the antibacterial activity was observed.

Ent-Copalic acid antibacterial and anti-biofilm properties against Actinomyces naeslundii and Peptostreptococcus anaerobius

Diterpenes are an important class of plant metabolites that can be used in the search for new antibacterial agents. ent-Copalic acid (CA), the major diterpene in Copaifera species exudates, displays several pharmacological properties. This study evaluates the CA antibacterial potential against the anaerobic bacteria Peptostreptococcus anaerobius and Actinomyces naeslundii. Antimicrobial assays included time-kill and biofilm inhibition and eradication assays. Time-kill assays conducted for CA concentrations between 6.25 and 12.5 μg/mL evidenced bactericidal activity within 72 h. CA combined with chlorhexidine dihydrochloride (CHD) exhibited bactericidal action against P. anaerobius within 6 h of incubation. As for A. naeslundii, the same combination reduced the number of microorganisms by over 3 log10 at 24 h and exerted a bactericidal effect at 48 h of incubation. CA at 500 and 2000 μg/mL inhibited P. anaerobius and A. naeslundii biofilm formation by at least 50%, respectively. CA at 62.5 and 1.000 μg/mL eradicated 99.9% of pre-formed P. anaerobius and A. naeslundii biofilms, respectively. These results indicated that CA presents in vitro antibacterial activity and is a potential biofilm inhibitory agent. This diterpene may play an important role in the search for novel sources of agents that can act against anaerobic bacteria.

Association, Distribution, Liberation, and Rheological Balances of Alkyldimethylbenzylammonium Chlorides (C12-C16).

It is known that cationic surfactants have an antimicrobial effect and act as enhancers. This paper studies three cationic surfactants from the group of alkyldimethylbenzylammonium chlorides (dodecyl-, tetradecyl-, and hexadecyl). Interest is focused on the association of the surfactants with respect to temperature, partition balances and their influence on drug release, rheological properties, and the pH of hydrogels. The critical micelle concentrations (CMC) of the surfactants were estimated from dependencies of conductivity, density, spectrofluorimetry, and UV–VIS spectrophotometry on molarity in the temperature range of 25–50 °C. It was found that the temperature dependence of a CMC is U-shaped, with its minimum at 30 °C, and the CMC value decreases as the length of the chain increases. The pseudo-phase separation model was used for the calculation of various thermodynamic parameters, such as the Gibbs free energies (spontaneous process), enthalpies (exothermic process), and entropies of the micelles’ formation, CMCs, and the degree of counterion binding. All thermodynamic parameters, as functions of the temperature, were estimated. It was found that partition coefficients increase as the length of the alkyl chain and the pH = (5.0–7.0) increase. The influences of surfactants, below and above the CMC, on drug (chlorhexidine dihydrochloride) release from hydrogels, rheological properties, and pH at 30 °C were studied. Also, the amounts of the released drug increase as the alkyl chains of the surfactants prolongate. The amounts of the released drug with the surfactant below the CMC are greater than that above the CMC. All hydrogels (regardless of the length of the alkyl chain) exhibit a non-Newtonian pseudo-plastic flow. The results obtained will be used in the formulation of the drug and surfactants into dosage forms.

Crystalline Polymorphism Emerging From a Milling-Induced Amorphous Form: The Case of Chlorhexidine Dihydrochloride

In this paper, solid-state amorphization induced by mechanical milling is shown to be a useful tool to explore the polymorphism of drugs and their mechanism of devitrification. We show in particular how the recrystallization of amorphous chlorhexidine dihydrochloride obtained by milling reveals a complex polymorphism that involves several polymorphic forms. Two new crystalline forms are identified, one of them appearing as a highly disordered precursor state which however clearly differs from the amorphous one. Several interpretations are here proposed to describe the puzzling nature of this phase. In addition, the possibility to amorphize chlorhexidine dihydrochloride by milling allowed to determine the main physical characters of the amorphous state which cannot be obtained through the usual thermal quench of the liquid because of a strong chemical degradation occurring on melting.

Diminished Antimicrobial Peptide and Antifungal Antibiotic Activities against Candida albicans in Denture Adhesive.

The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti-Candida activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.0% denture adhesive were incubated with Candida albicans strains ATCC 64124 and HMV4C in radial diffusion assays. In gels with 1.0% adhesive, HNP-1, HBD2, HBD3, IP-10, LL37 (only one strain), histatin 5 (only one strain), lactoferricin B, and SMAP28 showed diminished activity against C. albicans. In gels with 1.0% adhesive, amphotericin B and chlorhexidine dihydrochloride were active against both strains of C. albicans. These results suggest that denture adhesive may inactivate innate immune mediators in the oral cavity increasing the risk of C. albicans infections, but inclusion of antifungal antibiotics to denture adhesive may aid in prevention or treatment of Candida infections and denture stomatitis.

Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida Species Infections.

Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes. The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C. albicans ATCC 64124 or HMV4C were assessed in microdilution assays containing water or 1% denture adhesive. The minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) were determined. The cytotoxicities of denture adhesive compounded with these agents were assessed in 1.0 × 105 primary GE keratinocytes in LGM-3 media with resazurin. Lactoferricin B, SMAP28, sphingosine, dihydrosphingosine, and phytosphingosine in 1% denture adhesive lost antimicrobial activity for C. albicans (p < 0.05). Amphotericin B, chlorhexidine dihydrochloride, chlorhexidine gluconate, fluconazole, and nystatin in 1% denture adhesive or compounded directly into denture adhesive and then diluted to 1% adhesive, did not lose antimicrobial activity. Compounded formulations were not cytotoxic (LD50 > 100.0 μg/ml) against primary human GE keratinocytes. Antimicrobial peptides and antimicrobial lipids had diminished activities in 1% adhesive, suggesting that components in adhesives may inactivate local innate immune factors in the oral cavity, possibly predisposing denture wearers to Candida species infections. More importantly, antifungal agents retained their anti-C. albicans activities in denture adhesive, strongly suggesting that antifungal agents could be candidates for inclusion in adhesive formulations and used as prescribed topical treatments for individuals with denture stomatitis.

Polyolefin Microfiber Based Antibacterial Fibrous Membrane by Forced Assembly Coextrusion

There is a burgeoning demand for polyolefin based fibrous membranes with antibacterial properties due to the increasing awareness about recyclable materials for air and water purification. This paper presents a systematic study on the development of dual component, polypropylene (PP), and high density polyethylene (HDPE) fibrous membranes based on a continuous coextrusion and multiplication manufacturing technique. Chlorhexidine dihydrochloride (CHDH), an organic low molecular weight antibacterial additive, is melt-compounded to impart antibacterial characteristics to the fibrous membranes. The PP/HDPE membranes are hydrophobic and possess 77% porosity, whereas inclusion of CHDH increases the porosity to 91% and the surface area increases almost twofold. In addition, the membranes possess a mean flow pore size of 7 μm. ATR-FTIR study on the PP/CHDH/HDPE membranes indicate the presence of CHDH on the fiber surface, which imparts antibacterial character to the membrane. Investigations carried out on the CHDH containing PP/HDPE fibrous membranes using E. Coli indicate that the presence of CHDH on the fiber surface results in a bacterial growth inhibition zone on solid growth media. In addition, quantitative studies result in the complete reduction of colony forming units after 4 h of contact time.