Multimodal Positron Emission Tomography Imaging to Quantify Uptake of 89Zr-Labeled Liposomes in the Atherosclerotic Vessel Wall.

Nanotherapy has recently emerged as an experimental treatment option for atherosclerosis. To fulfill its promise, robust noninvasive imaging approaches for subject selection and treatment evaluation are warranted. To that end, we present here a positron emission tomography (PET)-based method for quantification of liposomal nanoparticle uptake in the atherosclerotic vessel wall. We evaluated a modular procedure to label liposomal nanoparticles with the radioisotope zirconium-89 (89Zr). Their biodistribution and vessel wall targeting in a rabbit atherosclerosis model was evaluated up to 15 days after intravenous injection by PET/computed tomography (CT) and PET/magnetic resonance imaging (PET/MRI). Vascular permeability was assessed in vivo using three-dimensional dynamic contrast-enhanced MRI (3D DCE-MRI) and ex vivo using near-infrared fluorescence (NIRF) imaging. The 89Zr-radiolabeled liposomes displayed a biodistribution pattern typical of long-circulating nanoparticles. Importantly, they markedly accumulated in atherosclerotic lesions in the abdominal aorta, as evident on PET/MRI and confirmed by autoradiography, and this uptake moderately correlated with vascular permeability. The method presented herein facilitates the development of nanotherapy for atherosclerotic disease as it provides a tool to screen for nanoparticle targeting in individual subjects' plaques.

Reversible Electroporation-Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89Zr-Labeled Reporter Nanoparticles.

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep.

Study of the Antibacterial Capacity of a Biomaterial of Zeolites Saturated with Copper Ions (Cu2+) and Supported with Copper Oxide (CuO) Nanoparticles.

In this work, copper (II) ions were saturated and copper oxide nanoparticles (CuO NPs) were supported in natural zeolite from Chile; this was achieved by making the adsorbent material come into contact with a copper ion precursor solution and using mechanical agitation, respectively. The kinetic and physicochemical process of the adsorption of copper ions in the zeolite was studied, as well as the effect of the addition of CuO NPs on the antibacterial properties. The results showed that the saturation of copper (II) ions in the zeolite is an efficient process, obtaining a 27 g L-1 concentration of copper ions in a time of 30 min. The TEM images showed that a good dispersion of the CuO NPs was obtained via mechanical stirring. The material effectively inhibited the growth of Gram-negative and Gram-positive bacteria that have shown resistance to methicillin and carbapenem. Furthermore, the zeolite saturated with copper at the same concentration had a better bactericidal effect than the zeolite supported with CuO NPs. The results suggested that the ease of processing and low cost of copper (II) ion-saturated zeolitic material could potentially be used for dental biomedical applications, either directly or as a bactericidal additive for 3D printing filaments.

Factors associated with scientific production citations in dentistry: Zero-inflated negative binomial regression and hurdle modelling.

Background: The global scientific literature in dentistry has shown important advances in the field, with major contributions ranging from the analysis of the basic epidemiological aspects of prevention to specialised results in the field of dental treatments. The present investigation aimed to analyse the current state of the scientific literature on dentistry hosted in the Web of Science database. Methods: The methodology included two phases in the analysis of articles and indexed reviews in all thematic areas. During the first phase, the following variables were analysed: scientific production by the publisher, the evolution of scientific output published by publishers, the factors associated with the impact of scientific production, and the modelling of the impact of scientific production on dentistry. During the second phase, associations, evolutions, and trends in the use of keywords in the scientific literature in dentistry were analysed. Results: The first phase shows that scientific production in dentistry will increase between 2010 and 2021, reaching 12,126 articles in 2021. Publishers such as Wiley and Elsevier stand out, but Quintessence Publishing has the most citations. Factors such as pages, authors, and references influence the number of citations. Phase 2 analyzes trends in the dental literature using the WoS database. Topics such as "dental education", "pediatric dentistry", and "pandemic" stand out. The intersection of technology and dentistry and the importance of evidence-based education are highlighted. Conclusions: In conclusion, the study shows that the most studied topics include the association of dental education and the curriculum, the association of pediatric dentistry with oral health, and dental care. The findings show that more recently emphasised topics also stand out, such as evidence-based dentistry, the COVID-19 pandemic, infection control, and endodontics, as well as the need for future research to expand current knowledge based on emerging topics in the scientific literature on dentistry.

Cytotoxicity of Peruvian propolis and Psidium guajava on human gingival fibroblasts, PBMCs and HeLa cells.

It is indisputable that every day it is demonstrated that natural products present diverse therapeutic benefits, which has boosted their incorporation within various products for clinical use. However, this must be accompanied by knowledge of their effect on cell lines to ensure their use is safe. The objective of this study was to evaluate the cytotoxic effect of two ethanolic extracts based on Peruvian natural products, on three human cell lines. Cervical cancer cell lines (HeLa), human gingival fibroblasts (HGF-1 - ATCC CRL-2014) (HGF-1) and peripheral blood mononuclear cells (PBMCs) were cultured and subsequently treated with preparations of ethanolic extracts of propolis (EEP) and Psidium guajava (EEG) from a concentration of 50 mg/mL to 0.024 mg/mL, by the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazole bromide reduction assay. At a concentration of 0.24 mg/mL EEG, viability of 99.7±1.24%, 99.8±2.2% and 99.7±2.7% was observed in HeLa, HGF-1 and PBMCs, respectively; >90% cell viability values were observed with EPP at 0.024 mg/mL, with HGF-1 showing the highest viability (96.9±1.15%). A dose-dependent effect was observed for both extracts with a decrease in cell viability as concentrations increased (up to 50 mg/mL). EEP and EEG extracts at low concentrations do not show cytotoxicity in human cell lines, these findings are an advance in the preclinical evaluation on their safety and open a continuity to further studies for their potential applications in dentistry and medicine.

The effect of biological and synthetic meshes on vaginal smooth muscle cell proliferation.

AIMS: To compare the effects of polypropylene mesh or porcine dermal acellular collagen matrix mesh with and without estradiol supplementation on vaginal smooth muscle cells (VaSMC) proliferation. RESULTS: Under in vitro culture conditions, VaSMC proliferation was significantly higher in the porcine dermal acellular collagen matrix mesh exposed cells compared to the type I polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.03 vs. 0.21 ± 0.01, P = 0.03). Under estradiol supplementation cell proliferation in the porcine mesh exposed cells remained significantly higher compared to the polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.04 vs. 0.15 ± 0.03, P < 0.01). CONCLUSION: The decreased rate of erosion found with the utilization of biological absorbable mesh in vaginal reconstructive surgery may partially be explained by the significantly increased VaSMC proliferation with porcine dermal acellular collagen mesh compared to polypropylene mesh.

Antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro oral biofilm.

Background: Natural products with antibacterial potential have begun to be tested on biofilm models, bringing us closer to understanding the response generated by the complex microbial ecosystems of the oral cavity. The objective of this study was to evaluate the antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro biofilm of Streptococcus gordonii and Fusobacterium nucleatum. Methods: The experimental work involved a consecutive, in vitro, longitudinal, and double-blinded study design. Propolis samples were collected from 13 different regions of the Peruvian Andes. The disk diffusion method was used for the antimicrobial susceptibility test. The cytotoxic effect of propolis on human gingival fibroblasts was determined by cell viability method using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the effect of propolis on the biofilm was evaluated by confocal microscopy and polymerase chain reaction (PCR). Results: The 0.78 mg/mL and 1.563 mg/mL concentrations of the methanolic fraction of the chloroform residue of Oxapampa propolis showed effects on biofilm thickness and the copy numbers of the srtA gene of S. gordonii and the radD gene of F. nucleatum at 48 and 120 hours, and chromatography (UV, λ 280 nm) identified rhamnocitrin, isorhamnetin, apigenin, kaempferol, diosmetin, acacetin, glycerol, and chrysoeriol. Conclusions: Of the 13 propolis evaluated, it was found that only the methanolic fraction of Oxapampa propolis showed antibacterial and antibiofilm effects without causing damage to human gingival fibroblasts. Likewise, when evaluating the chemical composition of this fraction, eight flavonoids were identified.

Freeze drying of polyelectrolyte complex nanoparticles: Effect of nanoparticle composition and cryoprotectant selection.

This work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG). The solid state of lyophilised powders was studied by thermal analysis and X-ray diffraction. Cytotoxicity studies were done by MTS assay and flow cytometry. The presence of a cryoprotectant was essential to achieve a successful powder reconstitution. The concentration of TRE was optimised for each type of PEC NPs. Protamine- and hyaluronate-based NPs reconstituted better than chitosan- and chondroitin sulphate-based NPs, respectively. PEG polymers were found to be more effective cryoprotectants than TRE and best results were achieved using co-freeze drying of NPs with TRE and PEG. These ternary NPs/TRE/PEG samples were crystalline, with expected better storage stability. PEG polymers were well tolerated by Caco-2 cells, with the exception of linear PEG 10 kDa. This work shows that, as regards the formulation design and maximising NP loading in the dried product, optimisation of the cryoprotectant type and content is needed as it is highly dependent not only on the type of polyelectrolyte pair in the PEC, but also the polyions ratio.

Antibacterial Effect of Hypochlorous Acid on Bacteria Associated with the Formation of Periodontal Biofilms: An in vitro Pilot Study

ABSTRACT Objective: To evaluate the antibacterial effect of electrolytically generated hypochlorous acid on Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. Material and Methods: In this in vitro experiment, the effect of hypochlorous acid (HOCl) on the strains S. gordonii, F. nucleatum, and P. gingivalis was evaluated using 4% sodium hypochlorite, 0.12% chlorhexidine, and distilled water as controls. The four groups were placed on each plate, and each group was replicated five times. The agar diffusion method by zones measurement was used. The data were processed with SPSS using the Kruskal-Wallis test and multiple comparison tests. Results: Hypochlorous acid showed an average inhibition halo of 9.28 mm on S. gordonii. As expected with distilled water, no zone of inhibition was noted for any of the bacteria, nor were zones of inhibition observed with HOCl for F. nucleatum and P. gingivalis. Conclusion: Hypochlorous acid showed antimicrobial properties against only S. gordonii and was less effective than 4% sodium hypochlorite and 0.12% chlorhexidine, although no significant differences were found between the latter.

Antibacterial and Antiadhesion Effects of Psidium guajava Fractions on a Multispecies Biofilm Associated with Periodontitis

Abstract Objective: To assess the antibacterial activity of Psidium guajava fractions and their effects on adhesion of a multispecies biofilm consisting of Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis in vitro. Material and Methods: Guava leaves were obtained from the mountains of northern Peru, where they grow wild and free of pesticides. The antimicrobial activity of 25 mg/mL petroleum ether, 25 mg/mL dichloromethane and 25 mg/mL methanol fractions of P. guajava was evaluated by measuring inhibition halos, as well as the effect on the adhesion of multispecies biofilms at 4, 7 and 10 days of growth by measuring the optical density. In addition, antimicrobial susceptibility was compared using the Kruskal-Wallis test and its multiple comparison tests, and differences in mean biofilm adhesion between each fraction were assessed by repeated measures analysis and the Tukey multiple comparison test. Results: The rank-based Kruskal-Wallis test highlighted differences in the effects of the fractions on the zone of inhibition for each oral bacterium, including S. gordonii (p=0.000), F. nucleatum (p=0.000), and P. gingivalis (p=0.000), the Tukey test showed that the group treated with 0.12% chlorhexidine exhibited the least amount of adhesion, followed by the group treated with the 1.56 mg/mL methanol fraction. Conclusion: The methanol fraction of P. guajava had an antibacterial effect on S. gordonii and P. gingivalis, and the 1.56 mg/mL methanol fraction decreased biofilm adhesion.

A systematic comparison of clinically viable nanomedicines targeting HMG-CoA reductase in inflammatory atherosclerosis.

Atherosclerosis is a leading cause of worldwide morbidity and mortality whose management could benefit from novel targeted therapeutics. Nanoparticles are emerging as targeted drug delivery systems in chronic inflammatory disorders. To optimally exploit nanomedicines, understanding their biological behavior is crucial for further development of clinically relevant and efficacious nanotherapeutics intended to reduce plaque inflammation. Here, three clinically relevant nanomedicines, i.e., high-density lipoprotein ([S]-HDL), polymeric micelles ([S]-PM), and liposomes ([S]-LIP), that are loaded with the HMG-CoA reductase inhibitor simvastatin [S], were evaluated in the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis. We systematically employed quantitative techniques, including in vivo positron emission tomography imaging, gamma counting, and flow cytometry to evaluate the biodistribution, nanomedicines' uptake by plaque-associated macrophages/monocytes, and their efficacy to reduce macrophage burden in atherosclerotic plaques. The three formulations demonstrated distinct biological behavior in Apoe-/- mice. While [S]-PM and [S]-LIP possessed longer circulation half-lives, the three platforms accumulated to similar levels in atherosclerotic plaques. Moreover, [S]-HDL and [S]-PM showed higher uptake by plaque macrophages in comparison to [S]-LIP, while [S]-PM demonstrated the highest uptake by Ly6Chigh monocytes. Among the three formulations, [S]-PM displayed the highest efficacy in reducing macrophage burden in advanced atherosclerotic plaques. In conclusion, our data demonstrate that [S]-PM is a promising targeted drug delivery system, which can be advanced for the treatment of atherosclerosis and other inflammatory disorders in the clinical settings. Our results also emphasize the importance of a thorough understanding of nanomedicines' biological performance, ranging from the whole body to the target cells, as well drug retention in the nanoparticles. Such systematic investigations would allow rational applications of nanomaterials', beyond cancer, facilitating the expansion of the nanomedicine horizon.

Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy.

The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter ((89)Zr-NRep) allows precise doxorubicin (DOX) quantification. Importantly, (89)Zr-NRep uptake also correlates with other types of nanoparticles' tumour accumulation. (89)Zr-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with >25 mg kg(-1) DOX accumulation in tumours had significantly better growth inhibition and enhanced survival. This non-invasive imaging tool may be developed into a robust inclusion criterion for patients amenable to nanotherapy.

Self-assembled hyaluronate/protamine polyelectrolyte nanoplexes: synthesis, stability, biocompatibility and potential use as peptide carriers.

This work investigates a new type of polyelectrolyte complex nanocarrier composed of hyaluronic acid (HA) and protamine (PROT). Small (approximately 60 nm) and negatively charged nanoparticles (NPs) with a polydispersity index of less than 0.2 were obtained with properties that were dependent on the mixing ratio, concentration of polyelectrolytes and molecular weight of HA. Salmon calcitonin (sCT) was efficiently (up to 100%) associated with the NPs, and the drug loading (9.6-39% w/w) was notably high, possibly due to an interaction between HA and sCT. The NPs released -70-80% of the sCT after 24 hours, with the estimated total amount of released sCT depending on the amount of HA and PROT present in the NPs. The isoelectric point of the NPs was close to pH 2, and the negative surface charge was maintained above this pH. The HA/PROT nanoplexes protected the sCT from enzymatic degradation and showed low toxicity to intestinal epithelial cells, and thus may be a promising oral delivery system for peptides.

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride.

BACKGROUND: Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells. METHODS: Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK) was studied using Western blot. RESULTS: We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK. CONCLUSION: A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate pharmacological and potentially toxicological effects of AgNPs and F on oral health.

Pegylation increases platelet biocompatibility of gold nanoparticles.

The increasing use of gold nanoparticles in medical diagnosis and treatment has raised the concern over their blood compatibility. The interactions of nanoparticles with blood components may lead to platelet aggregation and endothelial dysfunction. Therefore, medical applications of gold nanoparticles call for increased nanoparticle stability and biocompatibility. Functionalisation of nanoparticles with polythelene glycol (PEGylation) is known to modulate cell-particle interactions. Therefore, the aim of the current study was to investigate the effects of PEGylated-gold nanoparticles on human platelet function and endothelial cells in vitro. Gold nanoparticles, 15 nm in diameter, were synthesised in water using sodium citrate as a reducing and stabilising agent. Functionalised polyethylene glycol-based thiol polymers were used to coat and stabilise pre-synthesised gold nanoparticles. The interaction of gold nanoparticles-citrate and PEGylated-gold nanoparticles with human platelets was measured by Quartz Crystal Microbalance with Dissipation. Platelet-nanoparticles interaction was imaged using phase-contrast, scanning and transmission electron microscopy. The inflammatory effects of gold nanoparticles-citrate and PEGylated-gold nanoparticles in endothelial cells were measured by quantitative real time polymerase chain reaction. PEGylated-gold nanoparticles were stable under physiological conditions and PEGylated-gold nanoparticles-5400 and PEGylated-gold nanoparticles-10800 did not affect platelet aggregation as measured by Quartz Crystal Microbalance with Dissipation. In addition, PEGylated-gold nanoparticles did not induce an inflammatory response when incubated with endothelial cells. Therefore, this study shows that PEGylated-gold nanoparticles with a higher molecular weight of the polymer chain are both platelet- and endothelium-compatible making them attractive candidates for biomedical applications.

A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting.

UNLABELLED: Advances in preclinical molecular imaging have generated new opportunities to noninvasively visualize the biodistribution and tumor targeting of nanoparticle therapeutics. Capitalizing on recent achievements in this area, we sought to develop an (89)Zr-based labeling strategy for liposomal nanoparticles that accumulate in tumors via passive targeting mechanisms. METHODS: (89)Zr-labeled liposomes were prepared using 2 different approaches: click labeling and surface chelation. Pharmacokinetic and biodistribution studies, as well as PET/CT imaging of the radiolabeled nanoparticles, were performed on a mouse model of breast cancer. In addition, a dual PET/optical probe was prepared by incorporation of a near-infrared fluorophore and tested in vivo by PET and near-infrared fluorescence imaging. RESULTS: The surface chelation approach proved to be superior in terms of radiochemical yield and stability, as well as in vivo performance. Accumulation of these liposomes in tumor peaked at 24 h after injection and was measured to be 13.7 ± 1.8 percentage injected dose per gram. The in vivo performance of this probe was not essentially perturbed by the incorporation of a near-infrared fluorophore. CONCLUSION: We have developed a highly modular and efficient strategy for the labeling of liposomal nanoparticles with (89)Zr. In xenograft and orthotopic mouse models of breast cancer, we demonstrated that the biodistribution of these nanoparticles can be visualized by PET imaging. In combination with a near-infrared dye, these liposomal nanoparticles can serve as bimodal PET/optical imaging agents. The liposomes target malignant growth, and their bimodal features may be useful for simultaneous PET and intraoperative imaging.

Características clínicas y microbiológicas de pacientes con periodontitis agresiva generalizada / Clinical and microbiological characteristics of a patients with generalized aggressive periodontitis

RESUMEN: Objetivo: el objetivo de este estudio es describir las características clínicas y microbiológicas de una muestra de pacientes diagnosticados con periodontitis agresiva generalizada (PAgG). Materiales y métodos: En este estudio de corte transversal, 20 sujetos menores de 30 años con PAgG atendidos en las clínicas odontológicas de la Universidad de Antioquia en Medellín Colombia, fueron invitados a participar entre diciembre del 2015 y marzo del 2017, las muestras microbiológicas fueron analizadas usando técnicas de cultivo y tomadas en los seis sitios más profundos de cada paciente (≥ 5mm). Resultados: Prevotella ssp y F. nucleatum fueron detectados en altos porcentajes, Porphyromonas gingivalis (P.g) fue positivo para la mitad de los sujetos estudiados; además de los microorganismos comúnmente estudiados, el 10% de los pacientes fueron positivos para bacilos entéricos gram-negativos. Conclusiones: se observaron grandes proporciones de microorganismos que incluyeron Prevotella spss y F. nucleatum; el 10% de los pacientes fueron positivos para bacilos entéricos gram-negativos.

ABSTRACT: Aim: The aim of this study is to describe the clinical and microbiological characteristics of a sample of patients diagnosed with generalized aggressive periodontitis (PAgG). Materials and methods: In this cross-sectional study, 20 subjects under 30 years of age with PAgG treated at the dental clinics of the University of Antioquia in Medellín, Colombia were invited to participate between December 2015 and March 2017, the microbiological samples analyzed using culture techniques were taken at the six deepest sites of each patient (≥ 5mm). Results: Prevotella ssp and F. nucleatum were detected in high percentages, Porphyromonas gingivalis (P.g) was positive for half of the studied subjects; In addition to the microorganisms commonly studied, 10% of the patients were positive for gram-negative enteric bacilli. Conclusions: large proportions of microorganisms were observed, including Prevotella spss and F. nucleatum; 10% of the patients were positive for gram-negative enteric bacilli.

Exploring the assembly process and properties of novel crosslinker-free hyaluronate-based polyelectrolyte complex nanocarriers.

The aim of this work was to study the formulation of pharmaceutically relevant polyelectrolyte complex nanoparticles (NPs) composed of hyaluronic acid (HA) and chitosan (CS) containing no crosslinkers. The influence of polymer mixing ratio, concentration and molecular weight as well as the type of counterion in chitosan salt on properties of the resulting NPs was examined. Formulations and their components were studied by laser light scattering, viscosity, infrared spectroscopy and microscopy. Physical stability, isoelectric points and cytotoxicity of selected NPs were determined. By appropriate modification of HA molecular weight, stable and non-sedimenting NPs were successfully formed. Sonication was found to be an effective method to reduce the molecular weight of HA from 2882±25 to 176±4 kDa with no chemical changes in the HA structure observed. High molecular weight CS formed micron-sized entities at all compositions investigated. Positively and negatively charged NPs were obtained depending on the mixing ratio of the polymers, with CS glutamate NPs yielding more negatively charged particles compared to CS chloride NPs. The smallest NPs (149±11 nm) were formed using HA with molecular weight of 176 kDa. Cytotoxicity of NPs was dependent on environmental pH but HA was found to exert cytoprotective effects on Caco-2 cells.

The use of quartz crystal microbalance with dissipation (QCM-D) for studying nanoparticle-induced platelet aggregation.

Interactions between blood platelets and nanoparticles have both pharmacological and toxicological significance and may lead to platelet activation and aggregation. Platelet aggregation is usually studied using light aggregometer that neither mimics the conditions found in human microvasculature nor detects microaggregates. A new method for the measurement of platelet microaggregation under flow conditions using a commercially available quartz crystal microbalance with dissipation (QCM-D) has recently been developed. The aim of the current study was to investigate if QCM-D could be used for the measurement of nanoparticle-platelet interactions. Silica, polystyrene, and gold nanoparticles were tested. The interactions were also studied using light aggregometry and flow cytometry, which measured surface abundance of platelet receptors. Platelet activation was imaged using phase contrast and scanning helium ion microscopy. QCM-D was able to measure nanoparticle-induced platelet microaggregation for all nanoparticles tested at concentrations that were undetectable by light aggregometry and flow cytometry. Microaggregates were measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by phase contrast and scanning helium ion microscopy.

Polimorfismo genético como factor de riesgo en periodontitis crónica / Genetic polymorphism as a risk factor in chronic periodontitis

Fundamento: polimorfismos genéticos como el gen interleuquina uno que codifica para la hipersecreción de ciertas citoquinas a diferentes estímulos, favorece el establecimiento de la periodontitis. Objetivo: determinar la prevalencia de los genes interleuquina 1 y su asociación con periodontitis crónica en una población Colombiana. Métodos: se realizó una investigación de corte transversal, el universo estuvo compuesto por 108 pacientes. El diagnóstico de periodontitis crónica avanzada y moderada-leve se basó en criterios definidos con anterioridad. Los pacientes sin evidencia de estos diagnósticos periodontales se usaron como grupo control. Para la determinación del polimorfismo de los genes interleuquina 1 α y 1 β, se tomaron células epiteliales del carrillo de la mucosa bucal donde se utilizó un hisopo y un enjuague bucal. Resultados: la prevalencia de los genes interleuquina 1 α y β fueron superior en el grupo de pacientes con periodontitis avanzada, pero sin diferencias significativas con respecto a los otros grupos. Tampoco se observaron asociaciones estadísticas significativas entre los genes interleuquina 1 α y β con algún tipo de periodontitis. Conclusiones: no se observó asociación reveladora entre los genes interleuquina 1 α y β y periodontitis crónica, por lo tanto este polimorfismo no puede ser considerado un factor de riesgo para esa clase de periodontitis en esta población.

Background: genetic polymorphisms such as interleukin 1 gene coding for the hyper secretion of certain cytokines to different stimuli, favors the establishment of periodontitis. Objective: to determine the prevalence of interleukin 1 genes and their association with chronic periodontitis in a Colombian population. Methods: in this cross-sectional research, the universe was composed of 108 patients. The diagnosis of mild- moderate to advanced chronic periodontitis was based on pre-defined criteria. Patients with no evidence of these periodontal diagnoses were used as a control group. For determination of the polymorphism of interleukin genes 1 α and β, cheek epithelial cells of the oral mucosa were taken using a swab and a mouthwash. Results: the prevalence of interleukin-1 α and β genes was higher in the group of patients with advanced periodontitis, but no statistically significant differences were observed when compared to the other groups. No statistically significant associations between genes Interleukin 1 α and β with some form of periodontitis were observed. Conclusions: no statistically significant association between interleukin 1 α and β genes and chronic periodontitis was observed, therefore this polymorphism cannot be considered a risk factor for that kind of periodontitis in this population.