RESUMO
Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.
Assuntos
Aderência Bacteriana , Biofilmes , Implantes Dentários , Lipopeptídeos , Testes de Sensibilidade Microbiana , Titânio , Titânio/farmacologia , Titânio/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Aderência Bacteriana/efeitos dos fármacos , Implantes Dentários/microbiologia , Lipopeptídeos/farmacologia , Humanos , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Bacillus subtilis/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/fisiologia , Porphyromonas gingivalis/crescimento & desenvolvimento , Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Propriedades de Superfície , Fibroblastos/efeitos dos fármacos , Fusobacterium nucleatum/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Tensoativos/farmacologiaRESUMO
New bone cement type that combines Sr2 + /Mg2 + or Sr2 + /Zn2 + co-substituted nano-hydroxyapatite (n-HAs) with calcium phosphate dibasic and chitosan/gelatin polymers was developed to increase adhesion and cellular response. The cements were physicochemically described and tested in vitro using cell cultures. All cements exhibited quite hydrophilic and had high washout resistance. Cement releases Ca2 + , Mg2 + , Sr2 + , and Zn2 + in concentrations that are suitable for osteoblast proliferation and development. All of the cements stimulated cell proliferation in fibroblasts, endothelial cells, and osteoblasts, were non-cytotoxic, and produced apatite. Cements containing co-substituted n-HAs had excellent cytocompatibility, which improved osteoblast adhesion and cell proliferation. These cements had osteoinductive potential, stimulating extracellular matrix (ECM) mineralization and differentiation of MC3T3-E1 cells by increasing ALP and NO production. The ions Ca2 + , Mg2 + , Zn2 + , and Sr2 + appear to cooperate in promoting osteoblast function. The C3 cement (HA-SrMg5%), which was made up of n-HA co-substituted with 5 mol% Sr and 5 mol% Mg, showed exceptional osteoinductive capacity in terms of bone regeneration, indicating that this new bone cement could be a promising material for bone replacement.
Assuntos
Cimentos Ósseos , Durapatita , Durapatita/farmacologia , Cimentos Ósseos/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Magnésio/farmacologia , Magnésio/metabolismo , Estrôncio/farmacologia , Células Endoteliais/metabolismo , Fosfatos de Cálcio/metabolismo , Osteoblastos/metabolismo , Regeneração ÓsseaRESUMO
Breast cancer is the second cause of cancer death in women worldwide. The search for therapeutic and preventive alternatives has increased in recent years. One synthetic drug for patients with hormone receptor-positive tumours is tamoxifen citrate (TMX). Curcumin (Cur) is a natural compound that is being tested. Both were coupled with nanoscale-controlled and sustained release systems to increase the effectiveness of the treatment and reduce adverse effects. We produced a controlled release system based on uniaxial and coaxial polymeric nanofibers of polycaprolactone (PCL), alginate (Alg) and gelatine (Gel) for the transport and release of TMX and Cur, as a new alternative to breast cancer treatment. Nanofibers combining PCL-Alg and PCL-Gel were fabricated by the electrospinning technique and physicochemically characterised by thermal analysis, absorption spectroscopy in the infrared region and X-ray diffraction. Morphology and size were studied by scanning electron microscopy. Additionally, the release profile of TMX and Cur was obtained by UV-Vis spectroscopy. Additionally, the cytotoxic effect on breast cancer cell line MCF7 and peripheral-blood mononuclear cells (PBMCs) from a healthy donor were evaluated by a Resazurin reduction assay. These assays showed that PCL-TMX nanofiber was highly toxic to both cell types, while PCL-Cur was less toxic.
RESUMO
This paper reports on the development of nanoparticles aiming at the in vitro controlled release of simvastatin (SVT). The nanoparticles were prepared by the nanoprecipitation method with polymers Eudragit® FS30D (EDGFS) or Eudragit® NE30D (EDGNE). EDGFS+SVT nanoparticles showed mean size of 148.8 nm and entrapment efficiency of 76.4%, whereas EDGNE+SVT nanoparticles showed mean size of 105.0 nm and entrapment efficiency of 103.2%. Infrared absorption spectra demonstrated that SVT incorporated into the polymer matrix, especially EDGNE. Similarly, the differential scanning calorimeter (DSC) curve presented no endothermic peak of fusion, indicating that the system is amorphous and the drug is not in the crystalline state. The maintenance of SVT in the amorphous state may favors its solubilization in the target release sites. In the in vitro dissolution assay, the SVT incorporated into the EDGFS+SVT nanoparticles showed a rapid initial release, which may be related to the pH of the dissolution medium used. Regarding the EDGNE+SVT nanoparticles, the in vitro release occurred in a bimodal behavior, i.e., an initial "burst" followed by a sustained delivery, with the kinetics of drug release following Baker-Lonsdale's mathematical model. All these features suggest the nanoparticulate system's potential to modulate SVT delivery and enhance its bioavailability.
Assuntos
Sinvastatina/farmacologia , Nanopartículas/análise , Liberação Controlada de Fármacos , Técnicas In Vitro/classificação , Preparações Farmacêuticas/administração & dosagem , Dissolução/efeitos adversosRESUMO
Myocardial infarction triggers cellular events that starts with the activation of inflammatory response and fibrogenic pathways involved in cardiac tissue remodeling. Angiotensin-(1-7) (Ang-(1-7)) is an endogenous heptapeptide from the renin-angiotensin system with a cardioprotective role due to its anti-inflammatory and anti-fibrotic activities in cardiac cells. Although the beneficial aspects of Ang-(1-7) in animal models of cardiac ischemia have been reported, the molecular events underlying Ang-(1-7) cardioprotective effect remains elusive. This study investigated the impact of oral treatment with Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (HPßCD/Ang-(1-7)) on the cardiac proteome dysregulation due to experimental myocardial infarction. Wistar male rats were submitted to experimental myocardial infarction and treated daily with HPßCD/Ang-(1-7) during 7â¯days or 60â¯days by gavage. Our results showed that HPßCD/Ang-(1-7) treatment ameliorates the post-infarction condition due to the modulation of proteins that initially favor the resolution of inflammation and mitochondrial dysfunction. Moreover, this study reported for the first time that Ang-(1-7) treatment after experimental myocardial infarction leads to the downregulation of the C-X-C chemokine receptor type 4 (CXCR4). SIGNIFICANCE: Myocardial infarction triggers a sequence of cellular and molecular events that starts with an intense inflammatory response that is resolved in the proliferative phase. Prolonged inflammatory phase can lead to adverse cardiac repair and heart failure. In this context, we proposed a post-MI treatment using Ang-(1-7) included in HPßCD and administrated orally. We observed that HPßCD/Ang-(1-7) treatment led to CXCR4 downregulation, highlighting this C-X-C chemokine receptor as a potential therapeutic target for ischemic heart diseases.
Assuntos
Angiotensina I/farmacologia , Regulação para Baixo/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores CXCR4/biossíntese , Administração Oral , Animais , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Proteoma/metabolismo , Proteômica , Ratos , Ratos WistarRESUMO
PURPOSE: Dry socket (DS) is one the most common and symptomatic post-extraction complications; however, no consensus on its treatment has been reached. This study aimed to develop a novel dressing material for DS containing the phenolic agent guaiacol and evaluate its biological properties. METHODS: An inclusion complex of guaiacol and ß-cyclodextrin (Gu/ßcd) was prepared by freeze-drying. Its antibacterial activity over six oral bacteria was analyzed using the microdilution method, and its cytotoxicity in osteoblasts was assessed with the MTT assay. The alveolar healing process induced by Gu/ßcd was evaluated histologically after the treatment of DS in rats. RESULTS: ßcd complexation potentiated Gu's antibacterial effect and reduced its cytotoxicity in osteoblasts. Bone trabeculae were formed in the alveolar apices of rats treated with Gu/ßcd by day 7. On day 14, woven bone occupied the apical and middle thirds of the sockets; on day 21, the entire alveolus was filled by newly formed bone, which was in a more advanced stage of repair than the positive control (Alvogyl™). CONCLUSION: The improvement in Gu's biological properties in vitro and the rapid alveolar repair in comparison with Alvogyl™ in vivo demonstrated the benefits of the Gu/ßcd complex as a future alternative for the treatment of DS.
Assuntos
Antibacterianos/uso terapêutico , Alvéolo Seco/tratamento farmacológico , Guaiacol/uso terapêutico , Osteoblastos/efeitos dos fármacos , Infecção da Ferida Cirúrgica/prevenção & controle , beta-Ciclodextrinas/uso terapêutico , Processo Alveolar/patologia , Animais , Antibacterianos/administração & dosagem , Bandagens , Sobrevivência Celular/efeitos dos fármacos , Alvéolo Seco/complicações , Alvéolo Seco/diagnóstico por imagem , Alvéolo Seco/patologia , Guaiacol/administração & dosagem , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Ratos Wistar , beta-Ciclodextrinas/administração & dosagemRESUMO
The present work demonstrated an efficient cutaneous wound healing using Bixin-loaded polycaprolactone (PCL) nanofibers as a controlled delivery system. The influence of Bixin (Bix) content on PCL nanofiber, Bix-PCL1(2.5% w/w bix) and Bix-PCL2 (12.5% w/w bix) formation was investigated using electrical conductivity, attenuated total reflectance infrared spectroscopy, X-ray diffraction, thermal analysis, and scanning electronic microscopy. The results showed that a greater bixin concentration resulted in higher polymeric solution electrical conductivity. Moreover, higher polymeric solution electrical conductivity provides lower nanofibers in terms of average diameter than pure PCL nanofibers. In vitro release was largely governed by a diffusion-controlled mechanism. The initial Bixin release domain showed a burst release over the first 10 hours where approximately 30% and 40% of Bixin was released from Bix-PCL1 and Bix-PCL2 nanofibers, respectively. The second kinetic domain was comprised of a continuous and slow Bixin release that led to almost 100% of the Bixin being released within 14 days. The results on excisional wound model in induced diabetic mice indicated that the low concentration of Bixin released from loaded Bix-PCL nanofibers maintain the biological activity of Bixin and is efficient in accelerating the wound healing as well as in reducing the scar tissue area compared with pure PCL nanofibers. Therefore, soft material Bixin-loaded PCL nanofibers are a promising candidate for use in wound dressing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1938-1949, 2017.
Assuntos
Carotenoides , Diabetes Mellitus Experimental/tratamento farmacológico , Nanofibras , Pele/lesões , Cicatrização/efeitos dos fármacos , Células 3T3-L1 , Animais , Carotenoides/química , Carotenoides/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Masculino , Camundongos , Nanofibras/química , Nanofibras/uso terapêutico , Poliésteres/química , Poliésteres/farmacologia , Pele/metabolismo , Pele/patologiaRESUMO
BACKGROUND: Antimicrobial peptides (AMPs) have shown rapid and potent effect against planktonic bacteria. However, control of periodontopathic biofilms is a challenge even for AMPs. Thus, the present study evaluates in vitro antimicrobial activity of synthetic peptide LyeTxI and association compound LyeTxI/ß-cyclodextrin (ßCD) against multispecies biofilms. METHODS: Sensibility to LyeTxI and LyeTxI/ßCD was determined for planktonic Gram-negative periodontopathogens. Time-kill kinetic assay was performed at minimum inhibitory concentrations (MICs) in all planktonic strains. Multispecies biofilms were grown on pegs using a biofilm device and studied by scanning electron microscopy at 2, 5, and 10 days. Minimal biofilm eradication concentration (MBEC) was determined for 2- and 4-day multispecies biofilms. Metabolic activity of biofilms was determined by fluorometry study. RESULTS: Biofilms showed reproducible cell density on pegs of the biofilm device. LyeTxI and LyeTxI/ßCD were active against all strains tested at concentrations ≤62.5 µg/mL. Kinetic assays showed rapid bactericidal effect of LyeTxI against all periodontopathogens. MBECs of LyeTxI and LyeTxI/ßCD against multispecies 2-day biofilms were two-fold higher than MICs of cells shed from biofilms. LyeTxI was able to reduce multispecies 2-day metabolic activity by 90%. Multispecies 4-day biofilms were tolerant to all agents tested. CONCLUSIONS: LyeTxI and LyeTxI/ßCD are active against periodontopathic bacteria, showing rapid bactericidal effect and may be used to prevent biofilm development. In the future, AMPs could be therapeutic tools for treatment of periodontitis.
Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , Biofilmes/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Humanos , Cinética , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Periodontite/microbiologiaRESUMO
INTRODUCTION: Angiotensin-(1-7) is a key component of the Renin-Angiotensin System, which can counter-regulate several deleterious effects caused by angiotensin II. Due to the potential for therapeutic use, several of its actions are specifically described in patents. AREAS COVERED: In this review, the authors describe a plethora of therapeutic uses for Angiotensin-(1-7), claimed and supported by experimental evidence in patent documents and applications. EXPERT OPINION: The clinical potential of Angiotensin-(1-7) as a therapeutic agent to treat several pathologies is evidenced by the variety of patents and clinical trials involving this peptide. Cancer treatment is one of the most advanced therapeutic areas, but clinical studies are also available in several other areas, such as cardiovascular, hematological, transplantation, surgical and medical procedures.
Assuntos
Angiotensina I/uso terapêutico , Ensaios Clínicos como Assunto , Fragmentos de Peptídeos/uso terapêutico , Sistema Renina-Angiotensina/fisiologia , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Desenho de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto , Fragmentos de Peptídeos/metabolismoRESUMO
The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.