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1.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445073

RESUMO

Human immunodeficiency virus (HIV-1) is still a major problem, not only in developing countries but is also re-emerging in several developed countries, thus the development of new compounds able to inhibit the virus, either for prophylaxis or treatment, is still needed. Nanotechnology has provided the science community with several new tools for biomedical applications. G2-S16 is a polyanionic carbosilane dendrimer capable of inhibiting HIV-1 in vitro and in vivo by interacting directly with viral particles. One of the main barriers for HIV-1 eradication is the reservoirs created in primoinfection. These reservoirs, mainly in T cells, are untargetable by actual drugs or immune system. Thus, one approach is inhibiting HIV-1 from reaching these reservoir cells. In this context, macrophages play a main role as they can deliver viral particles to T cells establishing reservoirs. We showed that G2-S16 dendrimer is capable of inhibiting the infection from infected macrophages to healthy T CD4/CD8 lymphocytes by eliminating HIV-1 infectivity inside macrophages, so they are not able to carry infectious particles to other body locations, thus preventing the reservoirs from forming.


Assuntos
Alcanossulfonatos/farmacologia , Fármacos Anti-HIV/farmacologia , Dendrímeros/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Compostos de Organossilício/farmacologia , Silanos/farmacologia , Linhagem Celular , Células Cultivadas , Infecções por HIV/transmissão , Humanos , Macrófagos/virologia , Polieletrólitos/farmacologia
2.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281151

RESUMO

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.


Assuntos
RNA Interferente Pequeno/uso terapêutico , Silanos/farmacologia , Cátions , Sobrevivência Celular , Dicroísmo Circular , Dendrímeros/química , Dendrímeros/farmacologia , Terapia Genética/métodos , Humanos , Células MCF-7 , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Tamanho da Partícula , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA de Cadeia Dupla/genética , RNA Interferente Pequeno/genética , Silanos/química , Silanos/metabolismo
3.
J Nanobiotechnology ; 19(1): 65, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658029

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. RESULTS: We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1-50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. CONCLUSIONS: Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.


Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Dendrímeros/farmacologia , Nanotecnologia/métodos , Silanos/farmacologia , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Fibroblastos , Ganciclovir , Infecções por HIV , HIV-1 , Humanos , Polieletrólitos
4.
Eur J Med Chem ; 215: 113292, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33631696

RESUMO

Iminopyridine-decorated carbosilane metallodendrimers have recently emerged as a promising strategy in the treatment of cancer diseases. Their unique features such as the nanometric size, the multivalent nature and the structural perfection offer an extraordinary platform to explore structure-to-property relationships. Herein, we showcase the outstanding impact on the antitumor activity of a parameter not explored before: the iminopyridine substituents in meta position. New Cu(II) carbosilane metallodendrimers, bearing methyl or methoxy substituents in the pyridine ring, were synthesized and thoroughly characterized. Electron Paramagnetic Resonance (EPR) was exploited to unveil the properties of the metallodendrimers. This study confirmed the presence of different coordination modes of the Cu(II) ion (Cu-N2O2, Cu-N4 and Cu-O4), whose ratios were determined by the structural features of the dendritic molecules. These metallodendrimers exhibited IC50 values in the low micromolar range (<6 µM) in tumor cell lines such as HeLa and MCF-7. The subsequent in vitro assays on both healthy (PBMC) and tumor (U937) myeloid cells revealed two key facts which improved the cytotoxicity and selectivity of the metallodrug: First, maximizing the Cu-N2O2 coordination mode; second, adequately selecting the pair ring-substituent/metal-counterion. The most promising candidates, G1(-CH3)Cl (8) and G1(-OCH3)NO3(17), exhibited a substantial increase in the antitumor activity in U937 tumor cells, compared to the non-substituted counterparts, probably through two different ROS-production pathways.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Dendrímeros/farmacologia , Piridinas/farmacologia , Silanos/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Cobre/química , Dendrímeros/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Piridinas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Silanos/síntese química
5.
Int J Biol Macromol ; 163: 2457-2464, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32980415

RESUMO

A novel cellulosic fibre was extracted from the peduncle portion of the fish tail palm tree and the extracted fish tail palm fibre was treated with different concentrations (1%, 5%, and 9%) of silane solution. The characteristic analysis on chemical, functional, mechanical and surface property of the extracted fish tail palm fibres were investigated through chemical composition analysis, Fourier Transform InfraRed spectroscopy (FT-IR), single fibre tensile test, and Scanning Electron Microscopy (SEM). Chemical analysis results indicate that silane treatment improved the cellulose content of the fish tail palm fibre. The highest cellulose content of 72.51% was observed in the 9% silane treated fish tail palm fibre. Also, it improved crystallinity index value of 62.5% for 5% silane treated fibre, which is confirmed through the X-ray diffraction analysis. FT-IR result indicates the removal of hemicellulose at characteristic wavelength of 1745 cm-1 for 5% silane treated fish tail palm fibre. Tensile property of the silane treated fish tail palm fibre (1, 5, and 9%) shows an increased tensile strength of 7.3%, 12%, and 6.6% as compared to raw fish tail palm fibre. Moreover, this type of novel natural fibres can reduce the cost while offering competent performance during the polymer-based product development.


Assuntos
Arecaceae/química , Celulose/química , Silanos/farmacologia , Arecaceae/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Polímeros/química , Polissacarídeos/química , Silanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração/efeitos dos fármacos
6.
Eur J Med Chem ; 207: 112695, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882608

RESUMO

A family of heterofunctional Schiff base carbosilane metallodendrons with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) at the focal point and dimethylamino groups on the periphery are described. The new systems have proved their ability to interact with biological molecules such as Human Serum Albumin (HSA) without affecting its secondary structure and erythrocytes membranes, causing haemolysis in a dose and generation dependent way. The combination of two active functional groups in one single dendritic platform has shown a cooperative effect in the viability of HeLa and PC-3 cells, with the second generation derivative standing out as the most promising with the lowest IC50. Experiments focused on advanced prostate cancer have shown an antimetastasic activity for those metallodendrons, hindering the adhesion of cells in one of the main targets of metastasis, bones, and inhibiting cell migration. Finally, the second generation metallodendron with one single metal centre and four dimethylamino groups on the dendritic wedge, was selected for an ex vivo experiment in nude mice with advanced prostate cancer inhibiting the tumour growth in a 40% compared to control mice.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Rutênio/química , Rutênio/farmacologia , Silanos/química , Silanos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dendrímeros/química , Dendrímeros/farmacologia , Dendrímeros/uso terapêutico , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Nus , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Células PC-3 , Neoplasias da Próstata/patologia , Rutênio/uso terapêutico , Silanos/uso terapêutico
7.
Macromol Biosci ; 20(12): e2000193, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32812374

RESUMO

Surface-induced thrombosis is problematic in blood-contacting devices composed of silicones or polyurethanes (PUs). Poly(ethylene oxide)-silane amphiphiles (PEO-SA) are previously shown effective as surface modifying additives (SMAs) in silicones for enhanced thromboresistance. This study investigates PEO-SAs as SMAs in a PU at various concentrations: 5, 10, 25, 50, and 100 µmol g-1 PU. PEO-SA modified PUs are evaluated for their mechanical properties, water-driven surface restructuring, and adhesion resistance against a human fibrinogen (HF) solution as well as whole human blood. Stability is assessed by monitoring hydrophilicity, water uptake, and mass loss following air- or aqueous-conditioning. PEO-SA modified PUs do not demonstrate plasticization, as evidenced by minimal changes in glass transition temperature, modulus, tensile strength, and percent strain at break. These also show a concentration-dependent increase in hydrophilicity that is sustained following air- and aqueous-conditioning for concentrations ≥25 µmol g-1 . Additionally, water uptake and mass loss are minimal at all concentrations. Although protein resistance is not enhanced versus an HF solution, PEO-SA modified PUs have significantly reduced protein adsorption and platelet adhesion from human blood at concentrations ≥10 µmol g-1 . Overall, this study demonstrates the versatility of PEO-SAs as SMAs in PU, which leads to enhanced and sustained hydrophilicity as well as thromboresistance.


Assuntos
Materiais Biocompatíveis/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Polietilenoglicóis/química , Trombose/prevenção & controle , Adsorção/efeitos dos fármacos , Materiais Biocompatíveis/química , Fibrinogênio/química , Humanos , Polietilenoglicóis/farmacologia , Poliuretanos/química , Silanos/química , Silanos/farmacologia , Silicones/química , Propriedades de Superfície/efeitos dos fármacos , Resistência à Tração , Trombose/patologia , Água/química
8.
Sci Rep ; 10(1): 10970, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620785

RESUMO

To study the antimicrobial effects of quaternary ammonium silane (QAS) exposure on Streptococcus mutans and Lactobacillus acidophilus bacterial biofilms at different concentrations. Streptococcus mutans and Lactobacillus acidophilus biofilms were cultured on dentine disks, and incubated for bacterial adhesion for 3-days. Disks were treated with disinfectant (experimental QAS or control) and returned to culture for four days. Small-molecule drug discovery-suite was used to analyze QAS/Sortase-A active site. Cleavage of a synthetic fluorescent peptide substrate, was used to analyze inhibition of Sortase-A. Raman spectroscopy was performed and biofilms stained for confocal laser scanning microscopy (CLSM). Dentine disks that contained treated dual-species biofilms were examined using scanning electron microscopy (SEM). Analysis of DAPI within biofilms was performed using CLSM. Fatty acids in bacterial membranes were assessed with succinic-dehydrogenase assay along with time-kill assay. Sortase-A protein underwent conformational change due to QAS molecule during simulation, showing fluctuating alpha and beta strands. Spectroscopy revealed low carbohydrate intensities in 1% and 2% QAS. SEM images demonstrated absence of bacterial colonies after treatment. DAPI staining decreased with 1% QAS (p < 0.05). Fatty acid compositions of dual specie biofilm increased in both 1% and 2% QAS specimens (p < 0.05). Quaternary ammonium silane demonstrated to be a potent antibacterial cavity disinfectant and a plaque inhibitor and can be of potential significance in eliminating caries-forming bacteria.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Silanos/farmacologia , Aminoaciltransferases/antagonistas & inibidores , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cisteína Endopeptidases , Cárie Dentária/tratamento farmacológico , Cárie Dentária/microbiologia , Placa Dentária/tratamento farmacológico , Placa Dentária/microbiologia , Dentina/efeitos dos fármacos , Dentina/microbiologia , Dentina/ultraestrutura , Desinfetantes/farmacologia , Humanos , Técnicas In Vitro , Lactobacillus acidophilus/efeitos dos fármacos , Lactobacillus acidophilus/fisiologia , Microscopia Eletrônica de Varredura , Simulação de Acoplamento Molecular , Boca/microbiologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia
9.
Eur J Med Chem ; 199: 112414, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438200

RESUMO

In searching for efficient and selective antitumour drugs, a new family of carbosilane metallodendrimers functionalized with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) is reported. Experiments of the biophysical characterization showed an ability to interact with biological membranes, as well as with proteins (e.g. human serum albumin) without affecting their usual biological activity. These metallodendrimers possessed potent and selective anticancer activity in vitro in a panel of tumour cell lines. Importantly, the first generation metallodendrimer, bearing 4 Ru(II) complexes, was remarkably active towards resistant prostate cancer cells, inhibiting both cell proliferation and metastasis to bone tissues. Such promising antitumour activity can be further improved when given with docetaxel, with in vitro cytotoxicity being in the nanomolar range. Furthermore, its intravenous administration to an advanced prostate cancer mice model inhibited tumour growth up to 25% and 45% when given 10 mg/kg/week and 7.5 mg/kg/4-5 days, respectively.


Assuntos
Antineoplásicos/farmacologia , Ciclopentanos/farmacologia , Dendrímeros/farmacologia , Compostos Organometálicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Rutênio/farmacologia , Silanos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclopentanos/química , Dendrímeros/síntese química , Dendrímeros/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Rutênio/química , Silanos/química , Relação Estrutura-Atividade
10.
Mater Sci Eng C Mater Biol Appl ; 111: 110856, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279748

RESUMO

Refractory root canal infection of human teeth is the primary cause of dental treatment failure. Enterococcus faecalis is the major cause of refractory root canal infection. In the present study, poly(D,L-lactic-co-glycolide) (PLGA) submicron particles were used as carriers to deliver an antimicrobial quaternary ammonium silane (code-named K21) as well as calcium and phosphorus elements. The release profiles, antibacterial ability against E. faecalis, extent of infiltration into dentinal tubules, biocompatibility and in vitro mineralization potential of the particles were investigated. In addition, the antimicrobial effects of the particles against E. faecalis infection were evaluated in vivo in the teeth of beagle dogs. The encapsulated components were released from the PLGA particles in a sustained-release manner. The particles also displayed good biocompatibility, in vitro mineralization ability and antibacterial activity against E. faecalis. The particles could be driven into dentinal tubules of dentin slices by ultrasonic activation and inhibited E. faecalis colonization. In the root canals of beagle dogs, PLGA submicron particles loaded with K21, calcium and phosphorus demonstrated strong preventive effects against E. faecalis infection. The system may be developed into a new intracanal disinfectant for root canal treatment.


Assuntos
Cálcio/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Tamanho da Partícula , Fósforo/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Silanos/farmacologia , Dente/microbiologia , Animais , Antibacterianos/farmacologia , Linhagem Celular , Cães , Feminino , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Eletricidade Estática , Fosfatase Ácida Resistente a Tartarato/metabolismo , Dente/diagnóstico por imagem , Dente/patologia
11.
ACS Appl Mater Interfaces ; 12(20): 22433-22443, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32320193

RESUMO

Titanium implants in orthopedic applications can fail due to infection and impaired integration into the host. Most research efforts that facilitate osseointegration of the implant have not considered infection, and vice versa. Moreover, most infection control measures involve the use of conventional antibiotics which contributes to the global epidemic of antimicrobial resistance. Nitric oxide (NO) is a promising alternative to antibiotics, and while researchers have investigated NO releasing coatings, there are few reports on the function/robustness or the mechanism of NO release. Our comprehensive mechanistic study has allowed us to design, characterize, and optimize NO releasing coatings to achieve maximum antimicrobial efficacy toward bacteria with minimum cytotoxicity to human primary osteoblasts in vitro. As the antibiotic era is coming to an end and the future of infection control continues to demand new alternatives, the coatings described herein represent a promising therapeutic strategy for use in orthopedic surgeries.


Assuntos
Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Próteses e Implantes , Titânio/química , Antibacterianos/farmacologia , Compostos Azo/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Silanos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Molhabilidade
12.
Mater Sci Eng C Mater Biol Appl ; 110: 110742, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204050

RESUMO

To delay the degradation of magnesium alloys, silk fibroin as a natural organic polymer coating was fabricated on a 3-amino-propyltriethoxysilane (APTES) pretreated Mg-Zn-Ca alloy. APTES pretreatment coated the surface of magnesium alloys with amino groups, which can bond with functional groups in silk fibroin to form a compact coating/substrate interface. The influences of the APTES concentration and drying temperature on the coating adhesion and interface were investigated to explore the optimal parameters in the fabrication process. The nanoporous silk fibroin films completely covered the APTES pretreated Mg-Zn-Ca surface, which reached a thickness of ~7 µm. The chemical states for the coated Mg-Zn-Ca alloy were compared to those of the bare Mg-Zn-Ca alloy and the APTES pretreated Mg-Zn-Ca alloy to illustrate the coating mechanism. During in vitro degradation and electrochemical measurements in simulated body fluid (SBF), the samples with the silk fibroin coating showed remarkably improved corrosion resistance and a slower degradation rate compared to those of the bare samples, suggesting that the silk fibroin coating was an effective protection coating for the substrates and can delay the degradation of magnesium alloys. Moreover, a model for the in vitro degradation was proposed. In vitro cell experiments confirmed the excellent biocompatibility of silk fibroin coated Mg-Zn-Ca structure.


Assuntos
Ligas , Materiais Revestidos Biocompatíveis , Fibroínas , Teste de Materiais , Propilaminas , Silanos , Ligas/química , Ligas/farmacologia , Animais , Cálcio/química , Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Masculino , Manganês/química , Manganês/farmacologia , Camundongos , Porosidade , Propilaminas/química , Propilaminas/farmacologia , Silanos/química , Silanos/farmacologia , Zinco/química , Zinco/farmacologia
13.
Mater Sci Eng C Mater Biol Appl ; 110: 110647, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204077

RESUMO

Evaluation of the biological properties of silanized graphene oxide is important in the context of biomedical applications of the material. In this study, we have evaluated the toxicity, immunogenicity and other biological properties like osteogenicity of silanized graphene oxide (SiGO). Graphene oxide (GO) was silanized using a common silanizing agent namely (3-aminopropyl) triethoxysilane (APTES). Silanization was confirmed through infrared spectroscopy and elemental mapping. Post-silanization, we did not observe any significant changes in the morphology of GO. Silanization leads to an increase in the interlayer distance and disorder in the lattice. Study of in vitro toxicity of SiGO on three different cell lines namely primary human dermal fibroblast, murine embryonic fibroblast and human osteosarcoma cell lines revealed that toxicity of SiGO was significantly less than GO. We further showed that in vitro immune activation of macrophage was less in the case of SiGO in comparison to GO. Profiling of osteogenic differentiation of human mesenchymal stem cell revealed that SiGO is less osteogenic than GO. Study of acute toxicity in the murine model indicated that GO was hepatotoxic at experimental concentration whereas SiGO did not show any significant toxicity. This study implied that SiGO is a better biocompatible material than GO.


Assuntos
Materiais Biocompatíveis/farmacologia , Grafite/farmacologia , Silanos/farmacologia , Adulto , Fosfatase Alcalina/metabolismo , Animais , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Derme/citologia , Fibroblastos/efeitos dos fármacos , Grafite/toxicidade , Hemoglobinas/metabolismo , Humanos , Camundongos , Células NIH 3T3 , Tamanho do Órgão/efeitos dos fármacos , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Silanos/toxicidade , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Testes de Toxicidade , Difração de Raios X
14.
Mater Sci Eng C Mater Biol Appl ; 110: 110660, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204088

RESUMO

Bone-mimetic scaffolds are receiving much interest as such scaffolds exhibit excellent biocompatibility and very close mimic to bone structure and composition. Here, novel bone-mimetic nanohydroxyapatite (nHA)/collagen (Col) porous scaffolds (nHA/Col) were prepared from surface silanized mesoporous nanobioglass (NBG)/Col hybrid scaffold by biomimetic mineralization. Surface silanized mesoporous NBG was prepared by ultrasound-assisted sol-gel method and post treatment with 3-aminopropyltriethylsilane (APTS). The surface silanized mesoporous NBG was characterized by transmission electron microscopy (TEM), transmission electron microscopy-selected area electron diffraction (TEM-SAED) and X-ray photoelectron spectroscopy (XPS). The physicochemical/mechanical characterizations of the scaffolds included scanning electron microscopy (SEM) and TEM imaging of micro/nanostructure, energy dispersive X-ray (EDX) analysis of chemical composition, TEM-SAED and X-ray diffraction/Attenuated total Reflectance-Fourier Infrared spectroscopy (XRD/ATR-FTIR) analyses of amorphous-to-crystalline transformations, thermogravimetric/differential scanning calorimetric (TGA/DSC) analyses of thermal behaviour , porosity and dynamic mechanical analyses. The presence of NBG in collagen fibrillar network enabled progressive growth of HA nanocrystals and generation of a novel bone-mimetic hybrid structures while preserving the highly porous structure of collagen scaffold. The crystallinity, crystallite size and crystal morphology of the grown HA nanocrystals were controllable by regulation of the mineralization time. Furthermore, the osteogenic properties of the non-mineralized (NBG/Col) and mineralized (nHA/Col) hybrid porous scaffolds were examined in vivo using critical-sized calvarial bone defect model in rat. Histological and micro-computed tomography (Micro-CT) analyses after 6 weeks of implantation revealed that the mineralized scaffolds possess excellent in vivo osteogenic potential compared to the non-mineralized one. Collectively, by using surface silanized mesoporous NBG hybridization with collagen fibrillar network, we successfully introduced a new approach for developing novel bone-mimetic nanohydroxyapatite/collagen hybrid scaffolds that possess significant potential for bone tissue regeneration.


Assuntos
Materiais Biomiméticos/farmacologia , Osso e Ossos/efeitos dos fármacos , Cerâmica/farmacologia , Colágeno/farmacologia , Durapatita/farmacologia , Teste de Materiais , Silanos/farmacologia , Tecidos Suporte/química , Animais , Varredura Diferencial de Calorimetria , Colágeno/ultraestrutura , Osteogênese/efeitos dos fármacos , Espectroscopia Fotoeletrônica , Porosidade , Ratos , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Microtomografia por Raio-X
15.
ACS Appl Mater Interfaces ; 12(8): 9782-9789, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32011116

RESUMO

Thermochromic materials exhibit a color change in response to a change in temperature. Creating nontoxic microcapsules containing thermochromic materials for applications in ink and film materials is historically challenging. In this study, we develop a nontoxic chlorophenol red (CPR)-water thermochromic system and its microcapsules with silicone shells via a reaction between water and octadecyltrichlorosilane (OTS) at the interface of a w/o emulsion. The obtained microcapsules exhibit a clear color change with full reversibility and are successfully used as inks by screen printing and as additives in films. Nontoxicity of both microcapsules and films is demonstrated through cell cytotoxicity assays. These features make these novel materials applicable to the next generation of intelligent sensors, coating, and food packaging materials.


Assuntos
Teste de Materiais , Membranas Artificiais , Fenolsulfonaftaleína/análogos & derivados , Silanos , Silicones , Animais , Cápsulas , Camundongos , Células NIH 3T3 , Fenolsulfonaftaleína/química , Fenolsulfonaftaleína/farmacologia , Silanos/química , Silanos/farmacologia , Silicones/química , Silicones/farmacologia , Temperatura
16.
Int J Pharm ; 579: 119138, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061725

RESUMO

Glycodendrimers are a novel group of dendrimers (DDMs) characterized by surface modifications with various types of glycosides. It has been shown previously that such modifications significantly decrease the cytotoxicity of DDMs. Here, we present an investigation of glucose-modified carbosilane DDMs (first-third-generation, DDM1-3Glu) interactions with two models of biological structures: lipid membranes (liposomes) and serum protein (human serum albumin, HSA). The changes in lipid membrane fluidity with increasing concentration of DDMs was monitored by spectrofluorimetry and calorimetry methods. The influence of glycodendrimers on serum protein was investigated by monitoring changes in protein fluorescence intensity (fluorescence quenching) and as protein secondary structure alterations by circular dichroism spectrometry. Generally, all generations of DDMGlu induced a decrease of membrane fluidity and interacted weakly with HSA. Interestingly, in contrast to other dendritic type polymers, the extent of the DDM interaction with both biological models was not related to DDM generation. The most significant interaction with protein was shown in the case of DDM2Glu, whereas DDM1Glu induced the highest number of changes in membrane fluidity. In conclusion, our results suggest that the flexibility of a DDM molecule, as well as its typical structure (hydrophobic interior and hydrophilic surface) along with the formation of larger aggregates of DDM2-3Glu, significantly affect the type and extent of interaction with biological structures.


Assuntos
Dendrímeros/farmacologia , Portadores de Fármacos/farmacologia , Glucose/farmacologia , Albumina Sérica Humana/metabolismo , Silanos/farmacologia , Antineoplásicos/administração & dosagem , Dicroísmo Circular , Dendrímeros/química , Portadores de Fármacos/química , Glucose/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipossomos , Fluidez de Membrana/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Silanos/química , Espectrometria de Fluorescência
17.
J Biomed Mater Res A ; 108(5): 1086-1098, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31943702

RESUMO

Bacterial cellulose (BC) membranes display special properties and structures, thus attracting much attention in application in the biomedical areas, for example, as implants for bone or cartilage tissue engineering, as substitutes for skin repairing, and as supports for controlled drug delivery. However, native BC lacks the activity to inhibit bacteria growth on its surface, which limits its applications in biomedical fields. There have been reports on chemical modification of BC membranes to endow them with antimicrobial properties needed for some special biomedical applications. In the present study, aminoalkyl-grafted BC membranes were prepared by alkoxysilane polycondensation using 3-aminopropyltriethoxysilane (APTES). The characterization for morphology and chemical composition showed that BC membranes were successfully grafted with aminoalkylsilane groups through covalent bonding. The surface morphology and roughness of the membranes changed after chemical grafting. Furthermore, after grafting with APTES, the membranes got less hydrophilic than native BC. The aminoalkyl-grafted BC membranes showed strong antibacterial properties against Staphylococcus aureus and Escherichia coli and moreover, they were nontoxic to normal human dermal fibroblasts. These results indicate that aminoalkyl-grafted BC membranes are potential to be used for biomedical applications.


Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Celulose/análogos & derivados , Membranas Artificiais , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Celulose/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/prevenção & controle , Humanos , Propilaminas/química , Propilaminas/farmacologia , Silanos/química , Silanos/farmacologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos
18.
Future Med Chem ; 11(23): 3005-3013, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31710246

RESUMO

Aim: To research the synergistic activity of G2-S16 dendrimer and dapivirine (DPV) antiretroviral as microbicide candidate to prevent HIV-1 infection. Materials & methods: We assess the toxicity of DPV on cell lines by MTT assay, the anti-HIV-1 activity of G2-S16 and DPV alone or combined at several fixed ratios. Finally, their ability to inhibit the bacterial growth in vitro was assayed. The analysis of combinatorial effects and the effective concentrations were performed with CalcuSyn software. Conclusion: Our results represent the first proof-of-concept study of G2-S16/DPV combination to develop a safe microbicide.


Assuntos
Fármacos Anti-HIV/farmacologia , Dendrímeros/farmacologia , Células Epiteliais/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Pirimidinas/farmacologia , Silanos/farmacologia , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/toxicidade , Bactérias Anaeróbias/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Dendrímeros/administração & dosagem , Dendrímeros/toxicidade , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células Epiteliais/virologia , Infecções por HIV/prevenção & controle , Humanos , Testes de Sensibilidade Microbiana , Polieletrólitos , Polímeros , Pirimidinas/administração & dosagem , Pirimidinas/toxicidade , Silanos/administração & dosagem , Silanos/toxicidade , Células Vero
19.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426449

RESUMO

In recent years, there has become a growing need for the development of antifouling technology for application in the marine environment. The accumulation of large quantities of biomass on these surfaces cause substantial economic burdens within the marine industry, or adversely impact the performance of sensor technologies. Here, we present a study of transparent coatings with potential for applications on sensors or devices with optical windows. The focus of the study is on the abundance and diversity of biofouling organisms that accumulate on glass panels coated with novel transparent or opaque organically modified silicate (ORMOSIL) coatings. The diatom assessment was used to determine the effectiveness of the coatings against biofouling. Test panels were deployed in a marine environment in Galway Bay for durations of nine and thirteen months to examine differences in biofilm formation in both microfouling and macrofouling conditions. The most effective coating is one which consists of precursor, tetraethyl orthosilicate (HC006) that has a water contact angle > 100, without significant roughness (43.52 nm). However, improved roughness and wettability of a second coating, diethoxydimethylsilane (DMDEOS), showed real promise in relation to macrofouling reduction.


Assuntos
Biofilmes/efeitos dos fármacos , Diatomáceas/efeitos dos fármacos , Silanos/farmacologia , Organismos Aquáticos , Biofilmes/crescimento & desenvolvimento , Incrustação Biológica/prevenção & controle , Diatomáceas/crescimento & desenvolvimento , Transição de Fase , Silanos/química , Propriedades de Superfície/efeitos dos fármacos
20.
Nanoscale ; 11(28): 13330-13342, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31271405

RESUMO

Current cancer therapies present serious drawbacks including severe side-effects and development of drug resistance. Strategies based on nanosized metallodrugs combine the structural diversity and non-classical modes of action of metal complexes with the selectivity arising from the unique interaction of nanoparticles with biological membranes. A new family of water-soluble copper(ii) carbosilane metallodendrimers was synthesized and characterized as a nanotechnological alternative to current therapies. The interactions occurring over time between the dendrimers, at different generations (G0 to G2) and with different Cu(ii) counter-ions (nitrate vs. chloride), and cell-membrane models (cethyl-trimethylammonium bromide (CTAB) micelles and lecithin liposomes) were investigated using a computer-aided analysis of the electron paramagnetic resonance (EPR) spectra. The EPR analysis provided structural and dynamical information on the systems indicating that the increase in generation and the change of the Cu(ii) contra-ion - from nitrate to chloride - produce an increased relative amount and strength of interaction of the dendrimer with the model membranes. Interestingly, the stabilization effect produced a lower toxicity towards cancer cells. The cytotoxic effect of Cu(ii) metallodendrimers was verified by an in vitro screening in a selection of tumor cell lines, revealing the impact of multivalency on the effectivity and selectivity of the metallodrugs. As a proof-of-concept, first-generation dendrimer G1-Cu(ONO2)2 was selected for in-depth in vitro and in vivo antitumor evaluation towards resistant prostate cancer. The Cu(ii)-metallodendrimers produced a significant tumor size reduction with no signs of toxicity during the experiment, confirming their promising potential as anticancer metallodrugs.


Assuntos
Antineoplásicos , Membrana Celular , Cobre , Dendrímeros , Modelos Biológicos , Neoplasias Experimentais , Silanos , Animais , Membrana Celular/metabolismo , Membrana Celular/patologia , Cobre/química , Cobre/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , Dendrímeros/química , Dendrímeros/farmacologia , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células PC-3 , Silanos/química , Silanos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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