CHX Release Research Articles

Flowable resin-based composites modified with chlorhexidine-loaded mesoporous silica nanoparticles induce superior antibiofilm properties

Clinical failure of dental resin-composite restorations is mainly due to bacterial-mediated secondary caries formation. Therefore, the development of a flowable resin-composite material having inherent antibacterial properties is crucial to enhance the durability of dental restorations. Herein, dental flowable resin-composite material was modified with chlorhexidine-loaded mesoporous silica nanoparticles (CHX-MSN) to induce in situ antibacterial properties against S. mutans. Mesoporous silica nanoparticles loaded with chlorhexidine (CHX-MSN) were formulated and characterized for drug-loading/encapsulation efficiency, morphology by electron microscopy, and infrared spectral analysis. CHX-MSN were incorporated into the flowable composite material at different concentrations of 1, 5, and 10% (w/w) and examined at two time points (baseline and 3 months in artificial saliva). The CHX-MSN modified composites exhibited an initial CHX release burst followed by a steady release up to 30 days. The antimicrobial efficacy of the modified composites was evaluated by crystal violet assay, MTT assay, and confocal laser scanning microscopy. In addition to measuring the degree of conversion and cytotoxicity, the mechanical properties were characterized by surface microhardness and flexural strength. The modified composites demonstrated a significant increase in antimicrobial properties compared to the unmodified control (p < 0.05) which is dependent on the concentration of the CHX-MSN nanoparticles. In addition, the modified composites possessed acceptable biocompatibility without adversely affecting mechanical properties and degree of conversion up to 5% addition of CHX-MSN nanoparticles. This study introduced a protocol to develop resin-based flowable dental composite material having superior antibacterial property against cariogenic biofilms aiming for enhancing clinical longevity of dental restorations.Graphical

Development of Chlorhexidine-loaded Lipid Nanoparticles Incorporated in a Bioceramic Endodontic Sealer

IntroductionThis study aimed to assess BioRoot RCS (BR) incorporating liposomal chlorhexidine digluconate (CHX) for its antibacterial activity, drug release capacity, and physicochemical properties. MethodsDrug release of CHX liposomal formulations in combination with BR was evaluated spectrophotometrically and through mathematical release models for 30 days. A selected combination was evaluated for antimicrobial properties against Enterococcus faecalis biofilm growth on human dentin. Cytotoxicity was assessed following the ISO 10993-5:2019 standard on days 1, 3, and 7. Physicochemical properties were evaluated through setting time, Fourier transform infrared spectroscopy, solubility, contact angle, and film thickness. ResultsFrom BR, liposomal CHX released up to 7-fold higher CHX than CHX solution (P < .05), following a triphasic drug release pattern compared to the CHX solution, which followed a quasi-Fickian diffusion. BR combined with a selected liposomal CHX completely inhibited E. faecalis biofilm growth compared to the combination of BR with CHX solution and the control group (P < .05). Liposomal CHX decreased the contact angle (P < .05) and solubility but increased cytotoxicity (P < .05) of BR, staying above the ISO threshold. None of the other physicochemical characteristics tested differed from BR (P > .05). ConclusionThis liposomal formulation improved CHX release from BR, enhancing the antibacterial effectiveness. It presents a promising approach for local antibiofilm therapy in endodontics without substantially altering the physicochemical characteristics of BR.

Enhanced antimicrobial efficacy of chlorhexidine-encapsulated halloysite nanotubes incorporated in presurgical orthopedic appliances: an in vitro, controlled study.

Presurgical infant's orthopedic appliances (PSIOs) play an increasingly crucial role in the interdisciplinary management of neonatal CLP, aiming to improve and maintain adequate nasolabial aesthetics, followed by primary lip/nasal surgery in both unilateral and bilateral CLP cases. The use of PSIOs in cleft lip and palate patients can lead to contamination with oral microflora, acting as a potential reservoir for infectious microorganisms. Acrylic surfaces might provide retention niches for microorganisms to adhere, and inhabit, which is difficult to control in immunocompromised patients, thus predisposing them to increased infection risks. The objective of this multi-assay in vitro study was to investigate the effects of incorporating chlorhexidine-loaded halloysite nanotubes (CHX-HNTs) fillers on the morphological, cytotoxic, release, and antimicrobial characteristics of self-cured acrylic polymethyl methacrylate (PMMA) material used in pre-surgical orthopedic appliances. Disk-shaped PMMA specimens were prepared with varying proportions of CHX-HNTs. A control group without any addition served as a reference, and four experimental samples contained a range of different concentrations of CHX-HNTs (1.0, 1.5, 3, and 4.5 wt%). The antimicrobial efficacy was assessed using an agar diffusion test against common reference microorganisms: Candida albicans, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus agalactiae. Cytotoxicity was examined using the L929 cell line (mouse fibroblasts) through a (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, MTT) cell viability assay. The release kinetics of CHX were monitored using UV-spectral measurements. The statistical analysis used a one-way ANOVA followed by Tukey's post hoc test. The integration of CHX-HNTs in PMMA exhibited a substantial dose-dependent antifungal and antibacterial effect against microorganisms at tested mass fractions (1.0 to 4.5 wt%). CHX release was sustained for up to 60 days, supporting prolonged antimicrobial activity. Furthermore, no significant cytotoxicity was determined in the L929 fibroblast cell line (control), indicating the biocompatibility of the CHX-HNTs-enhanced PMMA. Incorporating CHX-HNTs in PMMA successfully enhanced its antimicrobial properties, providing sustained CHX release and superior antimicrobial efficacy. These findings demonstrate the potential of antimicrobial nanoparticles in dental therapies to improve therapeutic outcomes. However, rigorous further clinical trials and observational studies are warranted to validate the practical application, safety, and efficacy. This study has the potential to make a major impact on the health of infants born with cleft lip and palate by helping to reduce the prevalence of infectious illnesses. The incorporation of CHX-HNTs into PMMA-based appliances is a novel promising preventive approach to reduce microbial infections.

Microbiological, physicomechanical, and surface evaluation of an experimental self-curing acrylic resin containing halloysite nanotubes doped with chlorhexidine

ObjectiveThe objective was to synthesize halloysite nanotubes loaded with chlorhexidine (HNT/CHX) and evaluate the antimicrobial activity, microhardness, color change, and surface characteristics of an experimental self-curing acrylic resin containing varying concentrations of the synthesized nanomaterial. MethodsThe characterization of HNT/CHX was carried out by calculating incorporation efficiency, morphological and compositional, chemical and thermal evaluations. SAR disks were made containing 0 %, 3 %, 5 %, and 10 % of HNT/CHX. Specimens (n = 3) were immersed in distilled water and spectral measurements were carried out using UV/Vis spectroscopy to evaluate the release of CHX for up to 50 days. The antimicrobial activity of the composite against Candida albicans and Streptococcus mutans was evaluated by disk-diffusion test. Microhardness, color analyses (ΔE), and surface roughness (Ra) (n = 9) were performed before and after 30 days of immersion. Data were analyzed using ANOVA/Bonferroni. {Results.} The incorporation efficiency of CHX into HNT was of 8.15 %. All test groups showed controlled and cumulative CHX release up to 30 or 50 days. Significant antimicrobial activity was verified against both microorganisms (p < 0.001). After the 30-day immersion period, the 10 % HNT/CHX group showed a significant increase in hardness (p < 0.05) and a progressive color change (p < 0.001). At T0, the 5 % and 10 % groups exhibited Ra values similar to the control group (p > 0.05), while at T30, all groups showed similar roughness values (p > 0.05). {Significance.}The modification of a SAR with HNT/CHX provides antimicrobial effect and controlled release of CHX, however, the immediate surface roughness in the 3 % group was compromised when compared to the control group.

Silica nanoparticles containing nano-silver and chlorhexidine respond to pH to suppress biofilm acids and modulate biofilms toward a non-cariogenic composition

ObjectivesDental caries is caused by acids from biofilms. pH-sensitive nanoparticle carriers could achieve improved targeted effectiveness. The objectives of this study were to develop novel mesoporous silica nanoparticles carrying nanosilver and chlorhexidine (nMS-nAg-Chx), and investigate the inhibition of biofilms as well as the modulation of biofilm to suppress acidogenic and promote benign species for the first time. MethodsnMS-nAg was synthesized via a modified sol-gel method. Carboxylate group functionalized nMS-nAg (COOH-nMS-nAg) was prepared and Chx was added via electrostatic interaction. Minimal inhibitory concentration (MIC), inhibition zone, and growth curves were evaluated. Streptococcus mutans (S. mutans), Streptococcus gordonii (S. gordonii), and Streptococcus sanguinis (S. sanguinis) formed multispecies biofilms. Metabolic activity, biofilm lactic acid, exopolysaccharides (EPS), and TaqMan real-time polymerase chain reaction (RT-PCR) were tested. Biofilm structures and biomass were observed by scanning electron microscopy (SEM) and live/dead bacteria staining. ResultsnMS-nAg-Chx possessed pH-responsive properties, where Chx release increased at lower pH. nMS-nAg-Chx showed good biocompatibility. nMS-nAg-Chx exhibited a strong antibacterial function, reducing biofilm metabolic activity and lactic acid as compared to control (p < 0.05, n = 6). Moreso, biofilm biomass was dramatically suppressed in nMS-nAg-Chx groups. In control group, there was an increasing trend of S. mutans proportion in the multispecies biofilm, with S. mutans reaching 89.1% at 72 h. In sharp contrast, in nMS-nAg-Chx group of 25 μg/mL, the ratio of S. mutans dropped to 43.7% and the proportion of S. gordonii and S. sanguinis increased from 19.8% and 10.9 to 69.8% and 56.3%, correspondingly. ConclusionpH-sensitive nMS-nAg-Chx had potent antibacterial effects and modulated biofilm toward a non-cariogenic tendency, decreasing the cariogenic species nearly halved and increasing the benign species approximately twofold. nMS-nAg-Chx is promising for applications in mouth rinse and endodontic irrigants, and as fillers in resins to prevent caries.

Antibacterial and fluorescent clear aligner attachment resin modified with chlorhexidine loaded mesoporous silica nanoparticles and zinc oxide quantum dots

ObjectivesTo develop an antibacterial and fluorescent clear aligner attachment resin via the incorporation of chlorhexidine loaded pore-expanded mesoporous silica nanoparticles (CHX@pMSN) and amino-silane functionalized zinc oxide quantum dots (aZnOQDs), and to evaluate its antibacterial activity, fluorescence capability, esthetic properties, mechanical performance and biocompatibility. MethodsCHX@pMSN and aZnOQDs were incorporated into the commercial resin composites (Filtek Z350 XT, 3M) at different mass fractions, control group: Filtek; fluorescent attachment resin (FAR): Filtek + 3 wt% aZnOQDs; antibacterial and fluorescent attachment resin (AFAR)-1: Filtek + 3 wt% aZnOQDs + 1 wt% CHX@pMSN; AFAR-2: Filtek + 3 wt% aZnOQDs + 3 wt% CHX@pMSN; AFAR-3: Filtek + 3 wt% aZnOQDs + 5 wt% CHX@pMSN. CHX release, antibacterial activity, fluorescence capability, color change, stain resistance, degree of conversion, depth of cure, polymerization shrinkage, water sorption and solubility, softening in solvent, flexural strength, flexural modulus, shear bond strength, and cytotoxicity were evaluated comprehensively. ResultsCHX could be continuously released from the AFAR groups for up to 30 days. CFU, MTT, lactic acid production, SEM and CLSM evaluation showed AFAR-2 and AFAR-3 could effectively inhibit S. mutans biofilms even after 1-month aging. Only AFAR-3 showed clinically perceptible color change and all the experimental groups were not more susceptible to staining. AFAR-1 and AFAR-2 could suppress polymerization shrinkage and enhance the resistance to degradation without compromising other properties, including degree of conversion, water sorption and solubility, flexural strength, flexural modulus, and shear bond strength. Depth of cure of all the four experimental groups was significantly decreased (p < 0.05) but still within the ISO standard. CCK-8 assay and live/dead cell staining denied the cytotoxicity of experimental resins. Fluorescence intensity tests showed that FAR and AFAR-2 could emit strong yellowish fluorescence under the excitation of ultraviolet for up to six months. ConclusionsAFRA-2 possessed long-term antibiofilm activity, strong fluorescence capability and satisfying biocompatibility without compromising esthetic and mechanical properties. This study proposed a new strategy for reducing bacteria accumulation around the attachment, which is also promising in helping orthodontists to remove the attachment thoroughly and precisely.

A Novel Coating of Orthodontic Archwires with Chlorhexidine Hexametaphosphate Nanoparticles.

A solution of CHX-HMP nanoparticles with an overall concentration of 5 mM for both CHX and HMP was prepared, characterized (using atomic force microscope and Fourier transformation infrared spectroscopy), and used to coat orthodontic stainless steel (SSW) and NiTi archwires (NiTiW). The coated segments were characterized (using scanning electron microscopy SEM with energy dispersive X-ray spectrometry and field emission SEM) and subjected to the elusion assessment. After having their composition validated, the average size of the CHX-HMP NPs was assessed to be 51.21 nm, and the analysis revealed that the particles had both chlorine and phosphorus. After 30 minutes in the coating solution, NPs deposited on the surface of the SSW and NiTiW. A continuous release of soluble CHX in artificial saliva was detected from both SSW and NiTiW as long as the experiment lasted for 28 days without reaching a plateau. However, the release from coated NiTiW was significantly more than coated SSW at 7, 14, and 28 days. While at day 21, the release from coated SSW was slightly greater than that from the coated NiTiW. Orthodontic stainless steel and NiTi archwires can be successfully coated with CHX-HMP NPs and give sustained release of CHX along the examined period.

Release Profiles of Carvacrol or Chlorhexidine of PLA/Graphene Nanoplatelets Membranes Prepared Using Electrospinning and Solution Blow Spinning: A Comparative Study

Nanofibrous membranes are often the core components used to produce devices for a controlled release and are frequently prepared by electrospinning (ES). However, ES requires high production times and costs and is not easy to scale. Recently, solution blow spinning (SBS) has been proposed as an alternative technique for the production of nanofibrous membranes. In this study, a comparison between these two techniques is proposed. Poly (lactic acid)-based nanofibrous membranes were produced by electrospinning (ES) and solution blow spinning (SBS) in order to evaluate the different effect of liquid (carvacrol, CRV) or solid (chlorhexidine, CHX) molecules addition on the morphology, structural properties, and release behavior. The outcomes revealed that both ES and SBS nanofibrous mat allowed for obtaining a controlled release up to 500 h. In detail, the lower wettability of the SBS system allowed for slowing down the CRV release kinetics, compared to the one obtained for ES membranes. On the contrary, with SBS, a faster CHX release can be obtained due to its more hydrophilic behavior. Further, the addition of graphene nanoplatelets (GNP) led to a decrease in wettability and allowed for a slowing down of the release kinetics in the whole of the systems.

Synthesis, Drug Release, and Antibacterial Properties of Novel Dendritic CHX-SrCl2 and CHX-ZnCl2 Particles.

This work demonstrated for the first time the synthesis of novel chlorhexidine particles containing strontium and zinc, to provide an effective, affordable, and safe intervention in the treatment of recurrent infections found in Medicine and Dentistry. The CHX-SrCl2 and CHX-ZnCl2 particles were synthesized by co-precipitation of chlorhexidine diacetate (CHXD) and zinc chloride or strontium chloride, where particle size was manipulated by controlling processing time and temperature. The CHX-ZnCl2 and CHX-SrCl2 particles were characterized using SEM, FTIR, and XRD. UV-Vis using artificial saliva (pH 4 and pH 7) was used to measure the drug release and ICP-OES ion release. The antibacterial properties were examined against P. gingivalis, A. actinomycetemcomitans, and F. nucleatum subsp. Polymorphum, and cytotoxicity was evaluated using mouse fibroblast L929 cells. The novel particles were as safe as commercial CHXD, with antibacterial activity against a range of oral pathogens. UV-Vis results run in artificial saliva (pH 4 and pH 7) indicated a higher release rate in acidic rather than neutral conditions. The CHX-ZnCl2 particles provided the functionality of a smart Zinc and CHX release, with respect to environmental pH, allowing responsive antibacterial applications in the field of medicine and dentistry.

Formulation of pH-sensitive chlorhexidine-loaded/mesoporous silica nanoparticles modified experimental dentin adhesive

We formulated a pH-sensitive chlorhexidine-loaded mesoporous silica nanoparticles (MSN) modified with poly-(lactic-co-glycolic acid) (CHX-loaded/MSN-PLGA) and incorporated into experimental resin-based dentin adhesives at 5 and 10 wt%. Nanocarriers were characterized in terms of morphology, physicochemical features, spectral analyses, drug-release kinetics at varying pH and its effect on dentin-bound proteases was investigated. The modified dentin adhesives were characterized for cytotoxicity, antimicrobial activity, degree of conversion (DC) along with CHX release, micro-tensile bond strength (μTBS) and nano-leakage expression were studied at different pH values and storage time. CHX-loaded/MSN-PLGA nanocarriers exhibited a significant pH-dependent drug release behavior than CHX-loaded/MSN nanocarriers without PLGA modification. The highest percentage of CHX release was seen with 10 wt% CHX-loaded/MSN-PLGA doped adhesive at a pH of 5.0. CHX-loaded/MSN-PLGA modified adhesives exhibited more profound antibiofilm characteristics against S. mutans and more sustained CHX-release which was pH dependent. After 6 months in artificial saliva at varying pH, the 5 wt% CHX-loaded/MSN-PLGA doped adhesive showed excellent bonding under SEM/TEM, higher μTBS, and least nano-leakage expression. The pH-sensitive CHX-loaded/MSN-PLGA could be of crucial advantage for resin-dentin bonding applications especially in reduced pH microenvironment resulting from biofilm formation; and the activation of dentin-bound proteases as a consequence of acid etching and acidic content of bonding resin monomers.

Modification ofCeiba pentandracellulose for drug release applications

AbstractTubular fibers (raw and wax-free) fromCeiba pentandra(CP) were cross-linked with butane-1,2,3,4-tetracarboxylic acid (BTCA) at different concentrations to obtain a porous biodegradable medium for drug release applications. Chlorhexidine diacetate (CHX) was added to the cross-linked fibers for drug release studies. The Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy results indicated that the cross-linked fibers with a 5:1 fiber:BTCA ratio presented the higher cross-linking density. CHX was added at different concentrations (8% and 16% wt/wt); the elemental analysis indicated that CHX was loaded up to 7.99 wt%.In vitrostudies showed a burst release of CHX within the first 3 h. CHX release kinetics was described using several models, with the Korsmeyer–Peppas equation, which adjusted better to the experimental data. The results indicated that the CP fibers are a feasible material for drug release applications.

Antibacterial, drug delivery, and osteoinduction abilities of bioglass/chitosan scaffolds for dental applications

Treating dental infections requires removing the damaged tissue and inserting a filling material. Scaffolds are very successful in numerous biomedical applications, especially dental/bone substitution. Here, hematite-doped bioglass/chitosan scaffolds are investigated as an alternative implant system for delivering 2% chlorhexidine gluconate (CHX) to repair infected root canals as well as for evaluating their osteoinduction ability. The antibacterial activity of the fabricated scaffolds was assessed using the agar diffusion method. Furthermore, ex vivo antibacterial tests were performed in infected teeth using Enterococcus faecalis. CHX's in vitro release was determined in PBS after 1, 7, and 14 days. Their osteoinductive ability was determined using white male Wistar-Furth rats. The antibacterial results show an obvious behavioral difference between the pure CHX and the CHX-loaded scaffolds against E. faecalis. Moreover, the CHX release behavior from the CHX-loaded scaffolds depended on its concentration within the scaffolds. The presence of hematite (Fe2O3) enhanced drug release and completely eliminated bacterial growth after 14 days, as revealed by the in vitro drug release and antibacterial tests. Scaffold implantation resulted in remarkable osteoinduction for both scaffolds. This study illustrates that the prepared scaffolds show antibacterial, drug delivery, and osteoinduction abilities that could potentially be used in endodontic therapy.

Alginate films augmented with chlorhexidine hexametaphosphate particles provide sustained antimicrobial properties for application in wound care

All chronic wounds are colonised by bacteria; for some, colonisation progresses to become infection. Alginate wound dressings are used for highly exuding chronic wounds as they are very absorbent, taking up large quantities of exudate while maintaining a moist wound bed to support healing. Some alginate dressings are doped with antimicrobials, most commonly silver, but evidence regarding the efficacy of these is largely inconclusive. This manuscript describes the development and in vitro assessment of alginate materials doped with chlorhexidine hexametaphosphate (CHX-HMP), a sparingly soluble salt which when exposed to aqueous environments provides sustained release of the common antiseptic chlorhexidine. Comparator materials were a commercial silver alginate dressing material and an alginate doped with chlorhexidine digluconate (CHXdg). CHX-HMP alginates provided a dose-dependent CHX release which was sustained for over 14 days, whereas CHXdg alginates released limited CHX and this ceased within 24 h. CHX-HMP and silver alginates were efficacious against 5 major wound pathogens (MRSA, E. coli, P. aeruginosa, K. pneumoniae, A. baumannii) in a total viable count (TVC) and an agar diffusion zone of inhibition (ZOI) model. At baseline the silver alginate was more effective than the CHX-HMP alginate in the TVC assay but the CHX-HMP alginate was the more effective in the ZOI assay. After 7 days’ artificial aging the CHX-HMP alginate was more effective than the silver alginate for four of the five bacteria tested in both assays. These materials may ultimately find application in the development of wound dressings for chronic wounds that provide sustained antimicrobial protection.

Characterization on the reduction of burst release via biodegradable polymers from chlorhexidine-release on coated Foley urinary catheter by chlorhexidine-loaded micelles

In this work, chlorhexidine-loaded block copolymer was fabricated into micelles (CHX-micelles) and was then coated on foley urinary catheter by dip technique. The number cycles of coating were alternated the bilayers between (CHX-micelles) and poly(acrylic acid) which presented the suitable cycles of coating at 90 bilayers. This cycle of coating presented enough CHX quantity on coated catheter but their still showed burst CHX-release in early stage at first day. Hence, poly (lactic acid), PLA and poly (ϵ-caprolactone), PCL were also used to coat on top of 90 bilayers of catheter surface to reduce the burst release. The CHX quantity was then investigated on coated catheter and were studied the CHX-release. Results showed that the coated catheters at 90 bilayers and then coated the PLA and PCL presented the reduction of burst CHX-release from 80% to 42% for PLA coating and 38% for PCL. Moreover, coating PCL nanospheres (PCL-NS) on coated of 90 bilayers (CHX-micelles/PAA) can assist to reduce the burst release of CHX and prolonged the CHX-release up to two weeks. Thus, this strategy can be reduced the burst CHX-release on coated urinary catheter at early stage and can be prolonged the CHX-release.

Multilayer nanocoating of Foley urinary catheter by chlorhexidine-loaded nanoparticles for prolonged release and anti-infection of urinary tract

Two types of chlorhexidine-loaded nanoparticles (CHX-loaded nanoparticles) were prepared: poly(ethylene glycol)-block-poly(ε-caprolactone) micelles and poly(ε-caprolactone) nanospheres. They were prepared by the solvent evaporation method and were used to coat the Foley urinary catheters. The 90 bilayers of dip coating with chlorhexidine-micelles and the 40 cycles of spray coating with chlorhexidine-nanospheres were investigated. The coating provided the CHX content as high as 93.59 ± 9.14 μg/cm2 and the thickness of coating was 9.17 ± 0.08 μm. Coated catheters were also investigated in the in vitro chlorhexidine-release, antibacterial activity, and cytotoxicity. CHX release from the coated catheters was controlled. The bacteria proliferation was inhibited up to 28 days and showed the reduction of bacteria on the coated catheter surface. Coated catheters showed no biofilm on the surface. In addition, the cytotoxicity showed no cytotoxic effect from the coating. These nanocoating systems promoted potential uses for indwelling catheter and urinary tract infection.

Resin-Based Materials with Chlorhexidine-Loaded MCM-41: Surface Characteristics, Drug Release, and Antibiofilm Activity.

Poly(methyl methacrylate) resins containing chlorhexidine diacetate (CHX)-loaded mesoporous silicate MCM-41 have the ability to prevent Candida biofilm adhesion and growth over time. With the aim of increasing knowledge of the drug release and surface properties of these materials and their relationship with antibiofilm activity, in this paper an acrylic-based resin containing CHX-loaded spherical and narrow size silanized MCM-41 was prepared. Resins containing CHX but no filler were prepared as well and compared. Samples were characterized for polymerization degree, water sorption, and drug release. The sample capacity of inhibiting Candida biofilm adhesion and formation over time was evaluated. All samples were able to reduce the Candida biofilm mass over time. The resin containing CHX loaded into silanized MCM-41 mesopores resulted in less activity during the first 4 h but was able to maintain antibiofilm activity for a longer time. This effect was correlated to the prolonged CHX release and to the sample surface modifications observed after treatment with water and artificial saliva, evaluated by X-ray photoemission spectroscopy, scanning electron, and atomic force microscopies.

Antibacterial layer-by-layer coatings to control drug release from soft contact lenses material

In this study we investigated the possibility of using polyelectrolytes with antibacterial properties to form layer-by-layer (LbL) coatings on contact lens materials with the objective of controlling the release of ophthalmic drugs, while minimizing bacterial growth. A silicone-based hydrogel recently proposed by our group was chosen as a drug releasing soft contact lens (SCL) material and three drugs were tested: moxifloxacin hydrochloride (MXF), chlorhexidine diacetate monohydrate (CHX), and diclofenac sodium salt (DIC). Employed coatings involved combinations of sodium alginate (ALG), chitosan (CHI), sodium hyaluronate (HA) and polylysine hydrobromide (PLL), using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a cross-linking agent. Controlled release of DIC was achieved using two double layers of the following combinations: ALG/PLL (EDC), HA (EDC)/CHI and HA/PLL (EDC) + Drug. Furthermore, the physical properties of the coated lens material were kept, or even improved, and bacterial growth was reduced. In contrast, these coatings did not retard the release of MXF and CHX. The specificity of the barrier effect of these LbL films for DIC may be attributed to the formation of reversible interactions between DIC and the polyelectrolyte chains. A top layer of HA was needed to reduce the interaction with tear proteins. The in vivo efficacy of a contact lens coated with ALG/PLL (EDC)//HA and loaded with DIC was predicted using a simplified mathematical model to estimate the drug concentration in the tear fluid. The period of time during which the estimated concentration of DIC remained above the half-maximum inhibitory concentrations for the active enzymes in the process of inflammation, was at least double that obtained with the uncoated sample.

PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface

ObjectiveTo characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface. MethodsNanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined. ResultsThe results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research. SignificanceThis innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry.

Activity of Chlorhexidine Gluconate Loaded at Varying Polyelectrolyte Multilayers against Aggregatibacter Actinomycetemcomitans

Chlorhexidine gluconate (CHX) has a bactericidal effect to Aggregatibacter actinomycetemcomitans (Aa) which causes periodontal disease. Therefore the controlled loading and release of CHX from multilayer thin film is beneficial for the local treatment of periodontitis. This study used ten bilayers of PDADMAC/PSSMA and PDADMAC/AL and loaded CHX into each film. Both un-loaded and loaded thin films were analysed using UV-Vis spectroscopy and AFM. The loaded film was thicker and rougher than the un-loaded film for both PDADMAC/PSSMA and PDADMAC/AL film. The loaded films were released in H2O2 for 24 h, and UV-Vis spectroscopy was measured and compared with the standard calibration curve of CHX. Results indicated that PDADMAC/PSSMA released 0.00052 M and PDADMAC/AL released 0.00071 M respectively. Both the loaded films were tested for toxicity to Aa. Neither film killed all colonies of Aa, however they reduced colony growth by 99% compared to the blank condition.

Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatite

Nanohydroxyapatite possesses exceptional biocompatibility and bioactivity regarding bone cells and tissues, justifying its use as a coating material or as a bone substitute. Unfortunately, this feature may also encourage bacterial adhesion and biofilm formation. Surface functionalization with antimicrobials is a promising strategy to reduce the likelihood of bacterial infestation and colonization on medical devices. Chlorhexidine digluconate is a common and effective antimicrobial agent used for a wide range of medical applications. The purpose of this work was the development of a nanoHA biomaterial loaded with CHX to prevent surface bacterial accumulation and, simultaneously, with good cytocompatibility, for application in the medical field. CHX (5–1500mg/L) was loaded onto nanoHA discs and the materials were evaluated for CHX adsorption and release profile, physic-chemical features, antibacterial activity against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis, and cytocompatibility toward L929 fibroblasts. Results showed that the adsorption of CHX on nanoHA surface occurred by electrostatic interactions between the cationic group of CHX and the phosphate group of nanoHA. The release of CHX from CHX-loaded nanoHA showed a fast initial rate followed by a slower kinetics release, due to constraints caused by dilution and diffusion-limiting processes. NanoHA.50 to nanoHA.1500 showed strong anti-sessile activity, inhibiting bacterial adhesion and the biofilm formation. CHX-nanoHA caused a dose- and time-dependent inhibitory effect on the proliferation of fibroblasts for nanoHA.100 to nanoHA.1500. Cellular behavior on nanoHA.5 and nanoHA.50 was similar to control. Therefore, CHX-loaded nanoHA surfaces appear as a promising alternative to prevention of devices-related infections.