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Metal-organic frameworks (MOFs) are a class of crystalline porous materials with outstanding physical and chemical properties that make them suitable candidates in many fields, such as catalysis, sensing, energy production, and drug delivery. By combining MOFs with polymeric substrates, advanced functional materials are devised with excellent potential for biomedical applications. In this research, Zeolitic Imidazolate Framework 8 (ZIF-8), a zinc-based MOF, was selected together with cellulose, an almost inexhaustible polymeric raw material produced by nature, to prepare cellulose/ZIF-8 composite flat sheets via an in-situ growing single-step method in aqueous media. The composite materials were characterized by several techniques (IR, XRD, SEM, TGA, ICP, and BET) and their antibacterial activity as well as their biocompatibility in a mammalian model system were investigated. The cellulose/ZIF-8 samples remarkably inhibited the growth of Gram-positive and Gram-negative reference strains, and, notably, they proved to be effective against clinical isolates of Staphylococcus epidermidis and Pseudomonas aeruginosa presenting different antibiotic resistance profiles. As these pathogens are of primary importance in skin diseases and in the delayed healing of wounds, and the cellulose/ZIF-8 composites met the requirements of biological safety, the herein materials reveal a great potential for use as gauze pads in the management of wound infections.
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The development of polymeric fabrics with photoinduced antibacterial activity is important for different emerging applications, ranging from materials for medical and clinical practices to disinfection of objects for public use. In this work we prepared a series of cellulose acetate membranes, by means of phase inversion technique, introducing different additives in the starting polymeric solution. The loading of 5,10,15,20-tetraphenylporphyrin (TPP), a known photosensitizer, was considered to impart antibacterial photodynamic properties to the produced membranes. Besides, the addition of a surfactant (Pluronic F-127) allowed to modify the morphology of the membranes whereas the use of graphene oxide (GO) enabled further photo-activated antibacterial activity. The three additives were tested in various concentrations and in different combinations in order to carefully explore the effects of their mixing on the final photophysical and photodynamic properties. A complete structural/morphologycal characterization of the produced membranes has been performed, together with a detailed photophysical study of the TPP-containing samples, including absorption and emission features, excited state lifetime, singlet oxygen production, and confocal analysis. Their antibacterial activity has been assessed in vitro against S. aureus and E. coli, and the results demonstrated excellent bacterial inactivation for the membranes containing a combination of the three additives, revealing also a non-innocent role of the membrane porous structure in the final antibacterial capacity.
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The development of green, low cost and sustainable synthetic routes to produce metal nanoparticles is of outmost importance, as these materials fulfill large scale applications in a number of different areas. Herein, snail slime extracted from Helix Aspersa snails was successfully employed both as bio-reducing agent of silver nitrate and as bio-stabilizer of the obtained nanoparticles. Several trials were carried out by varying temperature, the volume of snail slime and the silver nitrate concentration to find the best biogenic pathway to produce silver nanoparticles. The best results were obtained when the synthesis was performed at room temperature and neutral pH. UV-Visible Spectroscopy, SEM-TEM and FTIR were used for a detailed characterization of the nanoparticles. The obtained nanoparticles are spherical, with mean diameters measured from TEM images ranging from 15 to 30 nm and stable over time. The role of proteins and glycoproteins in the biogenic production of silver nanoparticles was elucidated. Infrared spectra clearly showed the presence of proteins all around the silver core. The macromolecular shell is also responsible of the effectiveness of the synthesized AgNPs to inhibit Gram positive and Gram negative bacterial growth.
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Isatin and its derivatives are important heterocycles found in nature and present in numerous bioactive compounds which possess various biological activities. Moreover, it is an essential building block in organic synthesis. The discovery of novel compounds active against human pathogenic bacteria and fungi is an urgent need, and the isatin may represent the suitable scaffold in the design of biologically relevant antimicrobials. A small library of 18 isatin hybrids was synthetized and evaluated for their antimicrobial potential on three reference strains: S. aureus, E. coli, both important human pathogens infamous for causing community- and hospital-acquired severe systemic infections; and C. albicans, responsible for devastating invasive infections, mainly in immunocompromised individuals. The study highlighted two lead compounds, 6k and 6m, endowed with inhibitory activity against S. aureus at very low concentrations (39.12 and 24.83 µg/mL, respectively).
Assuntos
Anti-Infecciosos , Isatina , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Candida albicans , Escherichia coli , Humanos , Indóis/farmacologia , Isatina/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Relação Estrutura-AtividadeRESUMO
The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO3) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO3 nanoparticles. The number of nanoparticles loaded on the substrates was determined through Molecular Plasma-Atomic Emission Spectroscopy and is quite small, so it cannot be detected through X-ray diffraction analysis. It increases from HAPAA, to HA, to HAPEI, in agreement with the different values of zeta potential of the different substrates. HRTEM and STEM images show the dimensions of the nanoparticles are very small, less than 1 nm. In physiological solution HA support displays a greater tungsten cumulative release than HAPEI, despite its smaller loaded amount. Indeed, WO3 nanoparticles-functionalized HA exhibits a remarkable antibacterial activity against the Gram-positive Staphylococcus aureus in absence of cytotoxicity, which could be usefully exploited in the biomedical field.
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Advances in nanotechnology have opened up new horizons in nanomedicine through the synthesis of new composite nanomaterials able to tackle the growing drug resistance in bacterial strains. Among these, nanosilver antimicrobials sow promise for use in the treatment of bacterial infections. The use of polydopamine (PDA) as a biocompatible carrier for nanosilver is appealing; however, the synthesis and functionalization steps used to obtain Ag-PDA nanoparticles (NPs) are complex and require time-consuming cleanup processes. Post-synthesis treatment can also hinder the stability and applicability of the material, and dry, offline characterization is time-consuming and unrepresentative of real conditions. The optimization of Ag-PDA preparation and purification together with well-defined characterization are fundamental goals for the safe development of these new nanomaterials. In this paper, we show the use of field-flow fractionation with multi-angle light scattering and spectrophotometric detection to improve the synthesis and quality control of the production of Ag-PDA NPs. An ad hoc method was able to monitor particle growth in a TLC-like fashion; characterize the species obtained; and provide purified, isolated Ag-PDA nanoparticles, which proved to be biologically active as antibacterial agents, while achieving a short analysis time and being based on the use of green, cost-effective carriers such as water.
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Candida albicans and Staphylococcus aureus are common human pathogens, frequently isolated independently or co-isolated from bloodstream infections, and able to form dense polymicrobial biofilms on various medical devices resulting in strong resistance to conventionally used antimicrobials. New and innovative approaches are therefore needed to ensure the successful management of biofilm related infections. In this study, a chalcone-based derivative and a polycyclic anthracene-maleimide adduct, previously ascertained by us as inhibitors of C. albicans and S. aureus growths, respectively, were reconsidered in a new perspective by evaluating the efficacy of a combined treatment against a polymicrobial biofilm. Both quantitative and qualitative analyses were carried out to delve into their inhibitory potential on the polymicrobial population. Our results indicate that these newly identified antimicrobials are effective in reducing the biomass of the mixed C. albicans-S. aureus biofilm and the viability of fungal-bacterial cells within the polymicrobial community; in addition, confocal laser scanning microscopy demonstrates that the combined treatment thoroughly modifies the architecture of the dual-species biofilm.
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Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Chalconas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/química , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Chalconas/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy-promising results for the prevention of bone defect-related infections in orthopedic surgeries.
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Gelatin-based films enriched with snail slime are proposed as novel biodegradable and naturally bioadhesive patches for cutaneous drug delivery. Films (thickness range 163-248 µm) were stretchable and they adhered firmly onto the wetted skin, especially those with high amount (70% V/V) of snail slime extract. Fluconazole was selected as model drug and added to films containing the highest amount of snail slime. The presence of Fluconazole (4.53 ± 0.07% w/w) did not modify significantly the mechanical properties, the swelling degree and the bioadhesive performances of the films. Structural investigations demonstrated that the crystalline form III of the drug changed to the amorphous one, forming an amorphous solid dispersion. Moreover, snail slime prevented the drug recrystallization over time. In vitro permeation studies showed that film exhibited a cumulative drug concentration (over 60% in 24 h) similar to that of the control solution containing 20% w/V of ethanol. Fluconazole-loaded gelatin films proved to be effective towards clinical isolates of Candida spp. indicating that the drug maintained its remarkable antifungal activity once formulated into gelatin and snail slime-based films. In conclusion, snail slime, thanks to its peculiar composition, has proved to be responsible of optimal skin adhesion, film flexibility and of the formation of a supersaturating drug delivery system able to increase skin permeation.
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Gelatina , Preparações Farmacêuticas , Administração Cutânea , Sistemas de Liberação de Medicamentos , FluconazolRESUMO
Lactic acid bacteria (LAB) "fermentates" confer a beneficial effect on intestinal function. However, the ability of new fermentations to improve LAB broth activity in preventing pathogen-induced intestinal inflammation and barrier dysfunction has not yet been studied. The objective of this study was to determine if broths of LAB fermented with Eruca sativa or Barbarea verna seed extracts prevent gut barrier dysfunction and interleukin-8 (CXCL8) release in vitro in human intestinal Caco-2 cells infected with enterohemorrhagic Escherichia coli (EHEC) O157:H7. LAB broths were assayed for their effects on EHEC growth and on Caco-2 viability; thereafter, their biological properties were analysed in a co-culture system consisting of EHEC and Caco-2 cells. Caco-2 cells infected with EHEC significantly increased CXCL8 release, and decreased Trans-Epithelial Electrical Resistance (TEER), a barrier-integrity marker. Notably, when Caco-2 cells were treated with LAB broth enriched with E. sativa seed extract and thereafter infected, both CXCL8 expression and epithelial dysfunction reduced compared to in untreated cells. These results underline the beneficial effect of broths from LAB fermented with E. sativa seed extracts in gut barrier and inflammation after EHEC infection and reveal that these LAB broths can be used as functional bioactive compounds to regulate intestinal function.
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Brassicaceae/química , Escherichia coli O157/efeitos dos fármacos , Escherichia coli O157/crescimento & desenvolvimento , Fermentação , Gastroenterite/prevenção & controle , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lactobacillus acidophilus , Extratos Vegetais/farmacologia , Probióticos/farmacologia , Sementes/química , Antibacterianos , Barbarea/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Farmacorresistência Bacteriana , Impedância Elétrica , Infecções por Escherichia coli , Escherichia coli O157/patogenicidade , Gastroenterite/microbiologia , Humanos , Interleucina-8/metabolismo , Mucosa Intestinal/fisiologia , Fitoterapia , Extratos Vegetais/isolamento & purificaçãoRESUMO
Extensive documentation is available on plant essential oils as a potential source of antimicrobials, including natural drugs against Candida spp. Yeasts of the genus Candida are responsible for various clinical manifestations, from mucocutaneous overgrowth to bloodstream infections, whose incidence and mortality rates are increasing because of the expanding population of immunocompromised patients. In the last decade, although C. albicans is still regarded as the most common species, epidemiological data reveal that the global distribution of Candida spp. has changed, and non-albicans species of Candida are being increasingly isolated worldwide. The present study aimed to review the anti-Candida activity of essential oils collected from 100 species of the Lamiaceae family growing in the Mediterranean area and the Middle East. An overview is given on the most promising essential oils and constituents inhibiting Candida spp. growth, with a particular focus for those natural products able to reduce the expression of virulence factors, such as yeast-hyphal transition and biofilm formation. Based on current knowledge on members of the Lamiaceae family, future recommendations to strengthen the value of these essential oils as antimicrobial agents include pathogen selection, with an extension towards the new emerging Candida spp. and toxicological screening, as it cannot be taken for granted that plant-derived products are void of potential toxic and/or carcinogenic properties.
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At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.
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Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fenretinida/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas , Fenretinida/farmacologia , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacosRESUMO
Non-Escherichia coli Enterobacterales (NECE) can colonize the human gut and may present virulence determinants and phenotypes that represent severe heath concerns. Most information is available for virulent NECE strains, isolated from patients with an ongoing infection, while the commensal NECE population of healthy subjects is understudied. In this study, 32 NECE strains were isolated from the feces of 20 healthy adults. 16S rRNA gene sequencing and mass spectrometry attributed the isolates to Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter kobei, Citrobacter freundii, Citrobacter amalonaticus, Cronobacter sp., and Hafnia alvei, Morganella morganii, and Serratia liquefaciens. Multiplex PCR revealed that K. pneumoniae harbored virulence genes for adhesins (mrkD, ycfM, and kpn) and enterobactin (entB) and, in one case, also for yersiniabactin (ybtS, irp1, irp2, and fyuA). Virulence genes were less numerous in the other NECE species. Biofilm formation was spread across all the species, while curli and cellulose were mainly produced by Citrobacter and Enterobacter. Among the most common antibiotics, amoxicillin-clavulanic acid was the sole against which resistance was observed, only Klebsiella strains being susceptible. The NECE inhabiting the intestine of healthy subjects have traits that may pose a health threat, taking into account the possibility of horizontal gene transfer.
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Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterobacteriaceae/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia , Citrobacter/efeitos dos fármacos , Citrobacter/genética , Citrobacter/patogenicidade , Cronobacter/efeitos dos fármacos , Cronobacter/genética , Cronobacter/patogenicidade , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Enterobacter/patogenicidade , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidade , Microbioma Gastrointestinal/genética , Voluntários Saudáveis , Humanos , Klebsiella/efeitos dos fármacos , Klebsiella/genética , Klebsiella/patogenicidade , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Virulência/genética , Fatores de Virulência/genéticaRESUMO
Snail mucus is an attractive natural substance, which is increasingly used in cosmetic creams and syrups thanks to its emollient, moisturizing, protective and reparative properties. The aim of the present study was to explore the physicochemical properties of chitosan-based films added with snail mucus extracted from Helix Aspersa Muller. To this aim, chitosan films at different content of snail mucus were fabricated by simple solvent casting technique. The results of X-ray diffraction analyses, tensile mechanical tests, Infrared spectroscopy and thermogravimetry demonstrated that snail mucus addition strongly modifies the properties of chitosan films. In particular, it acted like a plasticizer enhancing films extensibility up to ten times and strongly improving their water barrier and bioadhesion properties, with a trend depending on Snail mucus content. Furthermore, it provides the films with antibacterial properties and enhanced cytocompatibility, yielding materials with tailored properties for specific requirements.
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Antibacterianos/farmacologia , Quitosana/química , Muco/química , Caramujos/química , Animais , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Análise Espectral , Vapor , TermogravimetriaRESUMO
In this paper, a small series of anthracene-maleimide-based compounds was prepared and evaluated to assess the antimicrobial potential of this polycyclic core, a scaffold previously unexplored for new antibiotic development. Some of the new compounds showed appreciable anti-Staphylococcus aureus activity, together with good safety profiles. In particular, compound 13 proved to be the most promising of the series, showing remarkable antimicrobial activity toward planktonic and sessile bacterial cells within a mature preformed biofilm. The mechanism of action seems to be related to the ability of this compound to interfere with bacterial membrane functionality, probably through the targeting of key enzymes responsible for membrane redox homeostasis and energy production. The data reported confirm the ability of this polycyclic nucleus to behave as a new "privileged structure", suitable to be further exploited in the antimicrobial field.
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Antracenos/química , Antibacterianos/síntese química , Maleimidas/química , Compostos Policíclicos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Membrana Externa Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Chlorocebus aethiops , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Células VeroRESUMO
Clofazimine (CLZ) is an antibiotic with a promising behavior against Gram-positive bacteria; however, the drug is completely insoluble in water and accumulates in fat tissues. We explored nanocarriers, labeled and not labeled with rhodamine, consisting of negatively charged sulfobutylether-ß-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking ßCyD with epichlorohydrin followed by sulfonation in a strongly alkaline aqueous medium. The oligomeric carrier has a MW of 53 kDa and forms small nanoparticles of a few tens of nm. With aqueous solutions containing a 25 mg/mL oligomeric carrier, we loaded up to 0.5 mg/mL of drug. The oligomers exhibited a 10-fold better loading capacity compared to monomers and formed nanoparticles with a size in the 20-60 nm range after drug loading. Circular dichroism confirmed encapsulation of the CLZ in the nanocarriers. All carriers with or without CLZ are not cytotoxic up to 1 µM, while CLZ alone is highly cytotoxic at the same concentration. The drug has IC50 values below 100 nM against S. epidermidis. The same holds true also for clinical isolates of S. epidermidis, some displaying MDR. So, the selectivity index significantly increased for CLZ/carrier systems compared to the drug alone. Taken all together, our results open new avenues for the clinical application of this antibiotic.
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Clofazimina/química , Clofazimina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Staphylococcus epidermidis/efeitos dos fármacos , beta-Ciclodextrinas/química , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Peso MolecularRESUMO
Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause several clinically relevant syndromes in both adults and neonates. Despite the availability of efficient anti-HSV agents, the search for new therapeutic approaches is highly encouraged due to the increasing drug resistance of virus strains. Medicinal plants represent a source of potential bioactive compounds. In this context we evaluated the anti-herpetic activity of Hemidesmus indicus (L.) R. Br., a plant widely used in traditional Indian medicine. The hydroalcoholic extract prepared from roots was characterized by NMR and HPLC analysis and assayed in vitro by CPE reduction and virus infectivity assays to define its anti-viral effect. The extract's mechanism of action was investigated by virucidal and time-of-addition assays and by in vitro α-glucosidase inhibitory assay. The extract exhibited a remarkable anti-herpetic activity at 100 mg/mL, at non-cytotoxic concentration, through multiple mechanisms: it reduced the infectivity of viral particles released from infected cells possibly through its anti-ER α-glucosidase inhibitory activity and it inhibited the beginning stage of HSV infection acting as a virucide agent and/or preventing virus attachment to the host cell surface.
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Hemidesmus/química , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Antivirais/farmacologia , Sobrevivência Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Células Vero , alfa-Glucosidases/metabolismoRESUMO
The development of new biomaterials able to favor bone formation and to inhibit bone abnormal resorption is mandatory to face the increasing number of age-related musculo-skeletal disorders. Moreover, the increasing antibiotic resistance of clinically important bacteria, which is among the main causes of implant failure, requires new antimicrobial systems. In this study, we prepared multifunctional materials consisting of hydroxyapatite-zoledronate composite crystals decorated with Ag Nanoparticles (AgNPs). Zoledronate, a potent bisphosphonate widely applied for the treatment of pathologies associated to abnormal bone loss, was incorporated into hydroxyapatite up to about 8â¯wt%. Loading of poly(ethylenimine) - stabilized AgNPs onto the crystals was promoted by zoledronate functionalization and provoked a significant variation of the values of zeta potential. The results of in vitro tests demonstrate that the multifunctional materials combine the beneficial actions of zoledronate and AgNPs. In fact, they improve osteoblast differentiation and activity, whereas they inhibit osteoclastogenesis and osteoclast differentiation, and significantly hinder the growth of multi-drug resistant Gram positive and Gram negative bacteria. As a consequence, they can be exploited both as antiresorptive agents and as antimicrobial materials able to prevent the development of bone-associated infections.
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Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas/química , Osteoclastos/efeitos dos fármacos , Prata/química , Materiais Biocompatíveis/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Difosfonatos/química , Difosfonatos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Imidazóis/química , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana/métodos , Osteoblastos/efeitos dos fármacos , Ácido ZoledrônicoRESUMO
In this work we developed new antibacterial composite materials using polydopamine (PDA) to trigger the deposition of silver nanoparticles (AgNPs) onto calcium phosphates, namely octacalcium phosphate (OCP) and α-tricalcium phosphate (αTCP). Functionalization of OCP and αTCP with a self-polymerized polydopamine layer was obtained by soaking the calcium phosphates in dopamine solution. The PDA surface of functionalized calcium phosphates (OCPd and αTCPd) promoted the deposition of AgNPs by reducing silver ions when soaked in a silver nitrate solution. The amount of deposited AgNPs can be modulated by varying the concentration of silver nitrate solution and the type of substrate. The results of in vitro tests carried out with osteoblast-like MG63 cells indicate that the combination of AgNPs with OCP provides more biocompatible materials than those obtained using αTCP as substrate. In particular, the study of osteoblast activity and differentiation was focused on the samples OCPdAg5 (silver content=8.2wt%) and αTCPdAg5 (silver content=4.7wt%), which did not show any cytotoxicity, and compared with those obtained on pure OCP and αTCP. The results demonstrate that the AgNPs loaded materials support osteoblast viability and differentiation, whereas they significantly inhibit the growth of relevant antibiotic-resistant pathogenic bacteria.
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Antibacterianos/síntese química , Biomimética , Fosfatos de Cálcio/química , Indóis/química , Polímeros/química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/química , Humanos , Nanopartículas/química , Osteoblastos/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Reação em Cadeia da Polimerase , Prata/química , Propriedades de SuperfícieRESUMO
The development of biomaterials able to act against a wide range of bacteria, including antibiotic resistant bacteria, is of great importance since bacterial colonization is one of the main causes of implant failure. In this work, we explored the possibility to functionalize hydroxyapatite (HA) nanocrystals with some monocyclic N-thio-substituted ß-lactams. To this aim, a series of non-polar azetidinones have been synthesized and characterized. The amount of azetidinones loaded on HA could be properly controlled on changing the polarity of the loading solution and it can reach values up to 17 wt%. Data on cumulative release in aqueous solution show different trends which can be related to the lipophilicity of the molecules and can be modulated by suitable groups on the azetidinone. The examined ß-lactams-HA composites display good antibacterial activity against reference Gram-positive and Gram-negative bacteria. However, the results of citotoxicity and antibacterial tests indicate that HA loaded with 4-acetoxy-1-(methylthio)-azetidin-2-one displays the best performance. In fact, this material strongly inhibited the bacterial growth of both methicillin resistant and methicillin susceptible clinical isolates of S. aureus from surgical bone biopsies, showing to be a very good candidate as a new functional biomaterial with enhanced antibacterial activity.