Profiling the plasmid conjugation potential of urinary Escherichia coli

Escherichia coli is often associated with urinary tract infection (UTI). Antibiotic resistance in E. coli is an ongoing challenge in managing UTI. Extrachromosomal elements – plasmids – are vectors for clinically relevant traits, such as antibiotic resistance, with conjugation being one of the main methods for horizontal propagation of plasmids in bacterial populations. Targeting of conjugation components has been proposed as a strategy to curb the spread of plasmid-borne antibiotic resistance. Understanding the types of conjugative systems present in urinary E. coli isolates is fundamental to assessing the viability of this strategy. In this study, we profile two well-studied conjugation systems (F-type and P-type) in the draft genomes of 65 urinary isolates of E. coli obtained from the bladder urine of adult women with and without UTI-like symptoms. Most of these isolates contained plasmids and we found that conjugation genes were abundant/ubiquitous, diverse and often associated with IncF plasmids. To validate conjugation of these urinary plasmids, the plasmids from two urinary isolates, UMB1223 (predicted to have F-type genes) and UMB1284 (predicted to have P-type genes), were transferred by conjugation into the K-12 E. coli strain MG1655. Overall, the findings of this study support the notion that care should be taken in targeting any individual component of a urinary E. coli isolate’s conjugation system, given the inherent mechanistic redundancy, gene diversity and different types of conjugation systems in this population

Characterizing Plasmids in Bacteria Species Relevant to Urinary Health

The urinary tract has a microbial community (the urinary microbiota or urobiota) that has been associated with human health. Whole genome sequencing of bacteria is a powerful tool, allowing investigation of the genomic content of the urobiota, also called the urinary microbiome (urobiome). Bacterial plasmids are a significant component of the urobiome yet are understudied. Because plasmids can be vectors and reservoirs for clinically relevant traits, they are important for urobiota dynamics and thus may have relevance to urinary health. In this project, we sought plasmids in 11 clinically relevant urinary species: Aerococcus urinae, Corynebacterium amycolatum, Enterococcus faecalis, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Lactobacillus gasseri, Lactobacillus jensenii, Staphylococcus epidermidis, Streptococcus anginosus, and Streptococcus mitis. We found evidence of plasmids in E. faecalis, E. coli, K. pneumoniae, S. epidermidis, and S. anginosus but insufficient evidence in other species sequenced thus far. Some identified plasmidic assemblies were predicted to have putative virulence and/or antibiotic resistance genes, although the majority of their annotated coding regions were of unknown predicted function. In this study, we report on plasmids from urinary species as a first step to understanding the role of plasmids in the bacterial urobiota. IMPORTANCE The microbial community of the urinary tract (urobiota) has been associated with human health. Whole genome sequencing of bacteria permits examination of urobiota genomes, including plasmids. Because plasmids are vectors and reservoirs for clinically relevant traits, they are important for urobiota dynamics and thus may have relevance to urinary health. Currently, urobiota plasmids are understudied. Here, we sought plasmids in 11 clinically relevant urinary species. We found evidence of plasmids in E. faecalis, E. coli, K. pneumoniae, S. epidermidis, and S. anginosus but insufficient evidence in the other 6 species. We identified putative virulence and/or antibiotic resistance genes in some of the plasmidic assemblies, but most of their annotated coding regions were of unknown function. This is a first step to understanding the role of plasmids in the bacterial urobiota

Genomic Survey of E. coli From the Bladders of Women With and Without Lower Urinary Tract Symptoms

Urinary tract infections (UTIs) are one of the most common human bacterial infections. While UTIs are commonly associated with colonization by Escherichia coli, members of this species also have been found within the bladder of individuals with no lower urinary tract symptoms (no LUTS), also known as asymptomatic bacteriuria. Prior studies have found that both uropathogenic E. coli (UPEC) strains and E. coli isolates that are not associated with UTIs encode for virulence factors. Thus, the reason(s) why E. coli sometimes causes UTI-like symptoms remain(s) elusive. In this study, the genomes of 66 E. coli isolates from adult female bladders were sequenced. These isolates were collected from four cohorts, including women: (1) without lower urinary tract symptoms, (2) overactive bladder symptoms, (3) urgency urinary incontinence, and (4) a clinical diagnosis of UTI. Comparative genomic analyses were conducted, including core and accessory genome analyses, virulence and motility gene analyses, and antibiotic resistance prediction and testing. We found that the genomic content of these 66 E. coli isolates does not correspond with the participant’s symptom status. We thus looked beyond the E. coli genomes to the composition of the entire urobiome and found that the presence of E. coli alone was not sufficient to distinguish between the urobiomes of individuals with UTI and those with no LUTS. Because E. coli presence, abundance, and genomic content appear to be weak predictors of UTI status, we hypothesize that UTI symptoms associated with detection of E. coli are more likely the result of urobiome composition

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Fractal analysis of the formation process and morphologies of hyaluronan/chitosan nanofilms in layer-by-layer assembly

In the last decade, hyaluronan (HA, polyanion) and chitosan (CHI, polycation) biopolymers have been assembled by layer-by-layer (LbL) for the synthesis of antibacterial coatings. As electrostatic interactions are the main driving force for the formation of LbL films, pH and ionic strength (IS) are important critical variables of synthesis. In this context, we used surface fractal analysis of HA/CHI films to characterize the growth process for different bilayers obtained with two pH (5 and 3) and IS values (0 and 0.1 M NaCl). Our results showed that the HA/CHI assembling is mainly affected by changes in the pH than IS. Fractal dimension (D-f) of pH 5 series presented values similar to 2.2, indicating that irregularities from the initial random adsorption process are minimized. However, when pH decreased to 3, D-f increases up to similar to 2.5, suggesting a transition to diffusion-limited aggregation

Urinary Plasmids Reduce Permissivity to Coliphage Infection

The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. While urinary Escherichia coli strains associated with urinary tract infection (UTI) and their phages have been catalogued for the urobiome, bacterium-plasmid-phage interactions have yet to be explored. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Putative F plasmids were predicted in 47 of 67 urinary E. coli isolates, and most of these plasmids carried genes that encode toxin-antitoxin (TA) modules, antibiotic resistance, and/or virulence. Urinary E. coli plasmids, from urinary microbiota strains UMB0928 and UMB1284, were conjugated into E. coli K-12 strains. These transconjugants included genes for antibiotic resistance and virulence, and they decreased permissivity to coliphage infection by the laboratory phage P1vir and the urinary phages Greed and Lust. Plasmids in one transconjugant were maintained in E. coli K-12 for up to 10 days in the absence of antibiotic resistance selection; this included the maintenance of the antibiotic resistance phenotype and decreased permissivity to phage. Finally, we discuss how F plasmids present in urinary E. coli strains could play a role in coliphage dynamics and the maintenance of antibiotic resistance in urinary E. coli. IMPORTANCE The urinary tract contains a resident microbial community called the urinary microbiota or urobiota. Evidence exists that it is associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. Bacterium-plasmid-phage interactions have been studied primarily in laboratory settings and are yet to be thoroughly tested in complex communities. This is especially true of the urinary tract, where the bacterial genetic determinants of phage infection are not well understood. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Urinary E. coli plasmids, encoding antibiotic resistance and transferred by conjugation into naive laboratory E. coli K-12 strains, decreased permissivity to coliphage infection. We propose a model by which urinary plasmids present in urinary E. coli strains could help to decrease phage infection susceptibility and maintain the antibiotic resistance of urinary E. coli. This has consequences for phage therapy, which could inadvertently select for plasmids that encode antibiotic resistance

Nanostructured porous silicon-mediated drug delivery

Sem informaçãoIntroduction: The particular properties of nanostructured porous silicon (nanoPS) make it an attractive material for controlled and localized release of therapeutics within the body, aiming at increased efficacy and reduced risks of potential side effects. Since this is a rapidly evolving field as a consequence of the number of research groups involved, a critical review of the state of the art is necessary. Areas covered: In this work, the most promising and successful applications of nanoPS in the field of drug delivery are reviewed and discussed. Two key issues such as drug loading and release are also analyzed in detail. The development of multifunctional (hybrid) systems, aiming at imparting additional functionalities to the nanoPS particles such as luminescence, magnetic response and/or plasmonic effects (allowing simultaneous tracking and guiding), is also examined. Expert opinion: Nanostructured materials based on silicon are promising platforms for pharmaceutical applications given their ability to degrade and low toxicity. However, a very limited number of clinical applications have been demonstrated so far. © 2014 Informa UK, Ltd.The particular properties of nanostructured porous silicon (nanoPS) make it an attractive material for controlled and localized release of therapeutics within the body, aiming at increased efficacy and reduced risks of potential side effects. Since this is a rapidly evolving field as a consequence of the number of research groups involved, a critical review of the state of the art is necessary. Areas covered: In this work, the most promising and successful applications of nanoPS in the field of drug delivery are reviewed and discussed. Two key issues such as drug loading and release are also analyzed in detail. The development of multifunctional (hybrid) systems, aiming at imparting additional functionalities to the nanoPS particles such as luminescence, magnetic response and/or plasmonic effects (allowing simultaneous tracking and guiding), is also examined. Expert opinion: Nanostructured materials based on silicon are promising platforms for pharmaceutical applications given their ability to degrade and low toxicity. However, a very limited number of clinical applications have been demonstrated so far.11812731283Sem informaçãoSem informaçãoSem informaçãoWest, J.L., Halas, N.J., Applications of nanotechnology to biotechnology (2000) Curr Opin Biotechnol, 11, pp. 215-217LaVan, D.A., McGuire, T., Langer, R., Small-scale systems for in vivo drug delivery (2003) Nat Biotechnol, 21, pp. 1184-1191Ozkan, M., Quantum dots and other nanoparticles: What can they offer to drug discovery? (2004) Drug Discov Today, 9, pp. 1065-1071Vaseashta, A., Dimova-Malinovska, D., Nanostructured and nanoscale devices, sensors and detectors (2005) Sci Tech Adv Mater, 6, pp. 312-318Wang, Y., Tang, Z., Kotov, N.A., Bioapplication of nanosemiconductors (2005) Mater Today, 8, pp. 20-31Wang, F., Tan, B.W., Zhang, Y., Luminescent nanomaterials for biological labeling (2006) Nanotechnology, 17, pp. R1-R13Korin, N., Kanapathipillai, M., Matthews, B.D., Shear-Activated nanotherapeutics for drug targeting to obstructed blood vessels (2012) Science, 337 (6095), pp. 738-742Holme, M.N., Fedotenko, I.A., Abegg, D., Shear-stress sensitive lenticular vesicles for targeted drug delivery (2012) Nat Nanotechnol, 7, pp. 536-543Hon, N.K., Shaposhnik, Z., Diebold, E.D., Tuning the biodegradability of silicon nanoparticles for drug delivery (2013) ECS Trans, 45 (8), pp. 7-12DeMuth, P., Hurley, M., Wu, C., Mesoscale porous silica as drug delivery vehicles: Synthesis characterization, and pH-sensitive release profiles (2011) Microporous Mesoporous Mater, 141 (1-3), pp. 128-134Stewart, M.P., Buriak, J.M., Chemical and biological applications of porous silicon technology (2000) Adv Mater, 12, pp. 859-869Jane, A., Dronov, R., Hodges, A., Porous silicon biosensors on the advance (2009) Trends Biotechnol, 27, pp. 230-239Martín-Palma, R.J., Manso, M., Torres-Costa, V., Optical biosensors based on semiconductor nanostructures (2009) Sensors, 9, pp. 5149-5172Canham, L.T., Bioactive silicon structure fabrication through nanoetching techniques (1995) Adv Mater, 7, pp. 1033-1037Anderson, S.H.C., Elliot, H., Wallis, D.J., Dissolution of different forms of partially porous silicon wafers under simulated physiological conditions (2003) Phys Stat Sol A, 197, pp. 331-335Sailor, M.J., Lee, E.J., Surface chemistry of luminescent silicon nanocrystallites (1997) Adv Mater, 9, pp. 783-793Canham, L.T., Reeves, C.L., Newet, J.P., Derivatized mesoporous silicon with dramatically improved stability in simulated human blood plasma (1999) Adv Mater, 11, pp. 1505-1507Martín-Palma, R.J., Manso-Silván, M., Torres-Costa, V., Biomedical applications of nanostructured porous silicon: A review (2010) J Nanophotonics, 4, p. 042502Santos, H.A., (2014) Porous silicon for biomedical applications, , Woodhead Publishing AmsterdamCanham, L.T., Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers (1990) Appl Phys Lett, 57, pp. 1046-1048Frohnhoff, S., Berger, M.G., Porous silicon superlattices (1994) Adv Mater, 6, pp. 963-965Loni, A., Canham, L.T., Berger, M., Porous silicon multilayer optical waveguides (1996) Thin Solid Films, 276, pp. 143-146Pellegrini, V., Tredicucci, A., Mazzoleni, C., Enhanced optical properties in porous silicon microcavities (1995) Phys Rev B, 52, pp. R14328-R14331Berger, M.G., Thonissen, M., Arens Fischer, R., Investigation and design of optical properties of porosity superlattices (1995) Thin Solid Films, 255, pp. 313-316Bisi, O., Ossicini, S., Pavesi, L., Porous silicon: A quantum sponge structure for silicon based optoelectronics (2000) Surf Sci Rep, 38, pp. 1-126Lehmann, V., (2002) Electrochemistry of silicon: Instrumentation science materials and applications, , Wiley-VCH, WeinheimSailor, M.J., (2012) Porous silicon in practice: Preparation characterization and applications, , Wiley-VCH, WeinheimCanham, L.T., Handbook of Porous Silicon, , (to be publishedRieger, M.M., Kohl, P.A., Mechanism of 111) silicon etching in HF-Acetonitrile (1995) J Electrochem Soc, 142, pp. 1490-1495Archer, R.J., Stain films on silicon (1960) J Phys Chem Solids, 14, pp. 104-110Saadoun, M., Mliki, N., Kaabi, H., Vapour-etching-based porous silicon: A new approach (2002) Thin Solid Films, 405, pp. 29-34Hummel, R.E., Chang, S.-S., Novel technique for preparing porous silicon (1992) Appl Phys Lett, 61, pp. 1965-1967Carstensen, J., Christophersen, M., Lolkes, S., Large area etching for porous semiconductors (2005) Phys Stat Sol (c, 2, p. 3339Smith, R.L., Collins, S.D., Porous silicon formation mechanisms (1992) J Appl Phys, 71, pp. R1-R22Foell, H., Christophersen, M., Carstensen, J., Formation and application of porous silicon (2002) Mater Sci Eng R, 39, pp. 93-141Canham, L.T., Aston, R., Will a chip every day keep the doctor away? (2001) Phys World, 14 (7), pp. 27-32Martín-Palma, R.J., Pascual, L., Herrero, P., Direct determination of grain sizes, lattice parameters, and mismatch of porous silicon (2002) Appl Phys Lett, 81, pp. 25-27Canham, L.T., Bioactive silicon structure fabrication through nanoetching techniques (1995) Adv Mater, 7, pp. 1033-1037Reffitt, D.M., Jugdaohsingh, R., Thompson, R.P.H., Silicic acid: Its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion (1999) J Inorg Biochem, 76, pp. 141-147Park, J.-H., Gu, L., Von Maltzahn, G., Biodegradable luminescent porous silicon nanoparticles for in vivo applications (2009) Nat Mater, 8, pp. 331-336Salonen, J., Kaukonen, A.M., Hirvonen, J., Mesoporous silicon in drug delivery applications (2008) J Pharm Sci, 97, pp. 632-653Gallach, D., Recio-Sánchez, G., Muñoz-Noval, A., Functionality of porous silicon particles: Surface modification for biomedical applications (2010) Mater Sci Eng B, 169, pp. 123-127Stewart, M.P., Buriak, J.M., Chemical and biological applications of porous silicon technology (2000) Adv Mater, 12, pp. 859-869Song, J.H., Sailor, M.J., Chemical modification of crystalline porous silicon surfaces (1999) Comments Inorg Chem, 21, pp. 69-84Naveas, N., Torres-Costa, V., Gallach, D., Chemical stabilization of porous silicon for enhanced biofunctionalization with immunoglobulin (2012) Sci Technol Adv Mater, 13 (4), p. 045009. , 7 ppBuriak, J.M., Organometallic chemistry on silicon and germanium surfaces (2002) Chem Rev, 102, pp. 1271-1308Salonen, J., Lehto, V.-P., Fabrication and chemical surface modification of mesoporous silicon for biomedical applications (2008) Chem Eng J, 137, pp. 162-172Anglin, E.J., Cheng, L., Freeman, W.R., Porous silicon in drug delivery devices and materials (2008) Adv Drug Del Rev, 60, pp. 1266-1277Anderson, R.C., Muller, R.S., Tobias, C.W., Chemical surface modification of porous silicon (1993) J Electrochem Soc, 140, pp. 1393-1396Salonen, J., Lehto, V.-P., Bjorkqvist, M., Studies of thermally-carbonized porous silicon surfaces (2000) Phys Stat Sol A, 182, pp. 123-126Tasciotti, E., Liu, X., Bhavane, R., Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications (2008) Nat Nanotechnol, 3, pp. 151-157Segal, E., Perelman, L.A., Cunin, F., Confinement of thermoresponsive hydrogels in nanostructured porous silicon dioxide templates (2007) Adv Funct Mater, 17 (7), pp. 1153-1162Mukherjee, P., Whitehead, M.A., Senter, R.A., Biorelevant mesoporous silicon/polymer composites: Directed assembly, disassembly, and controlled release (2006) Biomed Microdevices, 8 (1), pp. 9-15Hernández-Montelongo, J., Naveas, N., Degoutin, S., Porous siliconcyclodextrin based polymer composites for drug delivery applications (2014) Carbohydr Polym, 110, pp. 238-252Salonen, J., Laitinen, L., Kaukonen, A.M., Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs (2005) J Control Release, 108 (2-3), pp. 362-374Kaukonen, A.M., Laitinen, L., Salonen, J., Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles (2007) Eur J Pharm Biopharm, 66 (3), pp. 348-356Anglin, E.J., Schwartz, M.P., Ng, V.P., Engineering the chemistry and nanostructure of porous silicon fabrypérot films for loading and release of a steroid (2004) Langmuir, 20 (25), pp. 11264-11269Huotari, A., Xu, W., Monkäre, J., Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading, release and biological activity (2013) Int J Pharm, 454 (1), pp. 67-73Liu, D., Bimbo, L.M., Mäkilä, E., Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles (2013) J Control Release, 170 (2), pp. 268-278Haidary, S.M., Córcoles, E.P., Ali, N.K., Folic acid delivery device based on porous silicon nanoparticles synthesized by electrochemical etching (2013) Int J Electrochem Sci, 8, pp. 9956-9966Tzur-Balter, A., Gilert, A., Massad-Ivanir, N., Engineering porous silicon nanostructures as tunable carriers for mitoxantrone dihydrochloride (2013) Acta Biomater, 9 (4), pp. 6208-6217Chhablani, J., Nieto, A., Hou, H., Oxidized porous silicon particles covalently grafted with daunorubicin as a sustained intraocular drug delivery system (2013) Invest Ophthalmol Vis Sci, 54 (2), pp. 1268-1279Nieto, A., Hou, H., Sailor, M.J., Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles (2013) Exp Eye Res, 116, pp. 161-168Santos, H.A., Hirvonen, J., Nanostructured porous silicon materials: Potential candidates for improving drug delivery (2012) Nanomedicine, 7 (9), pp. 1281-1284Foraker, A.B., Walczak, R.J., Cohen, M.H., Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Caco-2 cell monolayers (2003) Pharm Res, 20, pp. 110-116Charnay, C., Bégu, S., Tourné-Péteilh, C., Inclusion of ibuprofen in mesoporous templated silica: Drug loading and release property (2004) Eur J Pharm Biopharm, 57, pp. 533-540Tzur-Balter, A., Young, J.M., Bonanno-Young, L.M., Mathematical modeling of drug release from nanostructured porous Si: Combining carrier erosion and hindered drug diffusion for predicting release kinetics (2013) Acta Biomater, 9, pp. 8346-8353Vaccari, L., Canton, D., Zaffaroni, N., Porous silicon as drug carrier for controlled delivery of doxorubicin anticancer agent (2006) Microelectron Eng, 83, pp. 1598-1601Bimbo, L.M., Mäkilä, E., Laaksonen, T., Drug permeation across intestinal epithelial cells using porous silicon nanoparticles (2011) Biomaterials, 32, pp. 2625-2633Sarparanta, M., Mäkilä, E., Heikkilä, T., 18F-labeled modified porous silicon particles for investigation of drug delivery carrier distribution in vivo with positron emission tomography (2011) Mol Pharm, 8, pp. 1799-1806Canham, L.T., Barnett, C.P., Bowditch, A.P., Implants for administering substances and methods of producing implant (1999) International, , patent WO9953898http://www.psivida.com/products-bracysil.html, Available fromKinnari, P.J., Hyvonen, M.L.K., Mäkilä, E.M., Tumour homing peptidefunctionalized porous silicon nanovectors for cancer therapy (2013) Biomaterials, 34, pp. 9134-9141Godin, B., Chiappini, C., Srinivasan, S., Discoidal porous silicon particles: Fabrication and biodistribution in breast cancer bearing mice (2012) Adv Funct Mater, 22, pp. 4225-4235Mann, A.P., Tanaka, T., Somasunderam, A., E-selectin-Targeted porous silicon particle for nanoparticle delivery to the bone marrow (2011) Adv Mater, 23 (36), pp. H278-H282Hernández, M., Recio, G., Martín-Palma, R.J., Surface enhanced fluorescence of anti-Tumoral drug emodin adsorbed on silver nanoparticles and loaded on porous silicon (2012) Nanoscale Res Lett, 7, p. 364Cheng, L., Anglin, E., Cunin, F., Intravitreal properties of porous silicon photonic crystals: A potential selfreporting intraocular drug-delivery vehicle (2008) Br J Ophthalmol, 92, pp. 705-711Hou, H., Nieto, A., Ma, F., Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon (2014) J Control Release, 178, pp. 46-54Muñoz-Noval, A., García, R., Ruiz-Casas, D., Design and characterization of biofunctional magnetic porous silicon flakes (2013) Acta Biomater, 9 (4), pp. 6169-6176Partial funding has been provided by the Comunidad de Madrid (Spain) under project Microseres

Antibacterial properties of chitosan-based coatings are affected by spacer-length and molecular weight

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORChitosan is a biopolymer with antibacterial properties, which are dependent on its molecular weight (Mw) and its degree of deacetylation (DDA). When grafted on surfaces as a coating, chitosan antibacterial efficiency is also dependent on the polymer chain conformation on the surface, as the amine groups, responsible of the antibacterial effect, should be available for contact with bacteria. To investigate this behavior, chitosans with different Mw were grafted onto plasma aminated surfaces through three different spacers: glutaric anhydride (GA), poly(ethylene-glycol) bis(carboxymethyl) ether (PEGb), and poly (ethylene-alt-maleic anhydride) (PA). The grafting efficiency was evaluated by X-ray Photoelectron Spectroscopy (XPS), contact angle and Rose Bengal test, while morphological features were assessed by profilometry analyses. Results evidenced a clear influence of the anchor arm length and of the Mw of chitosan both on the grafting efficiency and on the antibacterial behavior. PA CHIMW surface exhibited a better antibacterial response compared to GA and PEGb, which could be correlated to a denser coating coverage as seen by XPS and profilometry results. Further, PA CHIMW coating displayed a higher amine density, thus promoting the interaction with the bacteria cell wall. Based on these results, chitosan-based coatings can then be extended to a wide range of antibacterial applications.445478487CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIOR479486/2012-3249963/2013-22010/51748-72013/10957-02013/05135-12013/14888-3Procad 88882.151600/2017-01Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig