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1.
Chem Biol Interact ; 315: 108870, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669216

RESUMO

The toxic effects of poly(HEMA)-based polymeric nanoparticles must be analyzed before their biomedical applications as drug delivery systems. The aim of the study was to characterize and evaluate the toxicity for its biocompatibility of a newly synthesized l-glutamic acid-g-p(HEMA) polymeric nanoparticle The nanoparticle was synthesized with surfactant-free emulsion polymerization and grafting techniques. Grafting efficiency was estimated at 58%. The nanoparticle shape was verified as nearly spherical by scanning electron microscopy. Atomic force microscopy images showed a rough surface topography. The nanoparticle had an average size of ~194.6 nm on zeta analysis, and the zeta potential value was -18 mV. Fourier transformed infrared spectroscopy revealed spectra from 750 to 4000 cm-1 and characteristic peaks of stretching bands. The swelling ratio was 46%. With 24-h exposure, p(HEMA) and l-glutamic acid-g-p(HEMA) did not have cytotoxic effects on a human bronchial epithelial cell line (16HBE) and human monocyte cell line by water-soluble tetrazolium salt 1 (WST-1) assay and lactate dehydrogenase assay (LDH). It did not show genotoxic potential by comet assay and did not have mutagenic effects on Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains by Ames test. The nanoparticle at 160 µg/ml showed 2% hemolytic activity on erythrocytes. On cell migration assay, the percentage closure difference between exposed and control cells was estimated at 21%. We found no irritation effect on Hen's egg test-chorioallantoic membrane test. We determined that the polymeric nanoparticle l-glutamic acid-g-p(HEMA) was biocompatible and has potential for use in a drug delivery system.


Assuntos
Metacrilatos/química , Metacrilatos/toxicidade , Nanopartículas/química , Nanopartículas/toxicidade , Polímeros/química , Polímeros/toxicidade , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Linhagem Celular , Galinhas , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Emulsões/farmacologia , Emulsões/toxicidade , Eritrócitos/efeitos dos fármacos , Humanos , Monócitos/efeitos dos fármacos , Tamanho da Partícula , Coelhos , Salmonella typhimurium/efeitos dos fármacos , Propriedades de Superfície/efeitos dos fármacos , Tensoativos/química
2.
Carbohydr Polym ; 221: 84-93, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227170

RESUMO

In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ±â€¯1.3%) and high encapsulation efficiency (76.2 ±â€¯8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Quitosana/síntese química , Quitosana/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Etilenoglicóis/síntese química , Etilenoglicóis/química , Etilenoglicóis/toxicidade , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/toxicidade , Camundongos , Nanopartículas/toxicidade , Paclitaxel/farmacologia , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Toxicol In Vitro ; 60: 252-260, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195088

RESUMO

Universal adhesives are the most important innovation in restorative dentistry. They are composed of different monomers, solvents and fillers. The potential cytotoxic effect of these materials is an important scientific aspect in recent literature. The aim of this study was to determine, using different in vitro techniques, the cytotoxicity evaluation of seven universal enamel-dental adhesives on human gingival fibroblasts. For this purpose, seven universal dental enamel adhesives have been evaluated by in vitro cytotoxicity tests using direct contact tests (an unpolymerized and a polymerized method) and an indirect contact test: preparation of extracts. The polymerized method showed a cytotoxicity range from 36% (G-PremioBond, GPB) to 79% (FuturaBond M+, FB). With the unpolymerized direct methods the range was from 4% (Prime&Bond Active, PBA) to 40% (Ibond Universal, IB) for undiluted adhesives; generally passing to the major dilutions the test showed a strong inhibitory activity by all the adhesives. Whereas with the indirect method by diluting the extracts of all dental adhesives the cell viability increased. The data obtained from the work has shown a lower cytotoxic effect of Optibond Solo Plus (OB) and Adhesive Universal (AU) with more reliable results with the extracts technique. The choice of reliable in vitro cytotoxic technique could represent, in dental practice, an important aid for clinical procedures in the use of adhesive systems.


Assuntos
Cimentos Dentários/toxicidade , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Metacrilatos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos
4.
Oxid Med Cell Longev ; 2019: 3501059, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089407

RESUMO

Dental resin monomers such as 2-hydroxyethyl methacrylate (HEMA) disturb vital cell functions and induce mitochondrial intrinsic apoptosis via generation of oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the gene expression of antioxidative enzymes and plays a crucial role in the maintenance of cellular redox equilibrium and mitochondrial homeostasis. The present study investigated the functional significance of Nrf2 in cellular response toward HEMA. It was found that HEMA stimulation promoted nuclear translocation of Nrf2 and increased Nrf2 and heme oxygenase-1 (HO-1) expression, which was further enhanced by Nrf2 activator tert-butylhydroquinone (tBHQ), but suppressed by Nrf2 inhibitor ML385. Pretreatment of primary human dental pulp cells (hDPCs) with tBHQ protected the cells from HEMA-induced oxidative injury (increased reactive oxygen species production and apoptosis) and mitochondrial impairment (morphological alterations, decreased ATP production, suppressed oxidative phosphorylation activity, depolarization of mitochondrial membrane potential, and disrupted electron transport chain). In contrast, pretreatment with ML385 increased cell sensitivity to these injurious processes. This protective effect on mitochondria could be related to peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α)/nuclear respiratory factor 1 (NRF1) pathway. These results contribute to the understanding of the function of Nrf2 and the development of novel therapies to counteract the adverse effects of dental resin monomers.


Assuntos
Metacrilatos/toxicidade , Mitocôndrias/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/metabolismo , Adolescente , Adulto , Apoptose/efeitos dos fármacos , Polpa Dentária/patologia , Polpa Dentária/ultraestrutura , Heme Oxigenase-1/metabolismo , Humanos , Hidroquinonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Modelos Biológicos , Fator 1 Nuclear Respiratório/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
5.
Carbohydr Polym ; 217: 207-216, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079678

RESUMO

The design of functional materials capable of fighting fungal infections is of paramount importance given the intricate problem of multidrug-resistant pathogenic fungi. Herein, nanocomposites consisting of cross-linked poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) (PMETAC) and bacterial nanocellulose (BNC) were prepared, characterized and tested towards the polymorphic fungus Candida albicans. The BNC three-dimensional network enabled the in-situ polymerization of the non-toxic and bioactive quaternary-ammonium monomer, which originated transparent nanocomposites containing 10 and 40 wt.% of cross-linked PMETAC. Furthermore, the nanocomposites exhibit UV-A and UV-B blocking properties, high water-uptake capacity, thermal stability up to 200 °C, good viscoelastic (storage modulus > 1.7 GPa) and mechanical (Young's modulus ≥2.4 GPa) properties and are non-cytotoxic to human keratinocytes (HaCaT cells). The fungal inactivation reached a 4.4 ± 0.14-log CFU reduction for the nanocomposite containing only 10 wt.% of cross-linked PMETAC. Hence, these bioactive and non-cytotoxic materials can constitute potentially effective systems for the treatment of C. albicans infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Celulose/química , Metacrilatos/farmacologia , Nanocompostos/química , Antifúngicos/química , Antifúngicos/toxicidade , Linhagem Celular , Celulose/toxicidade , Humanos , Metacrilatos/química , Metacrilatos/toxicidade , Testes de Sensibilidade Microbiana , Nanocompostos/toxicidade , Temperatura Ambiente , Resistência à Tração , Água/química
6.
Nat Chem ; 11(6): 578-586, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30988414

RESUMO

Polymerization reactions conducted inside cells must be compatible with the complex intracellular environment, which contains numerous molecules and functional groups that could potentially prevent or quench polymerization reactions. Here we report a strategy for directly synthesizing unnatural polymers in cells through free radical photopolymerization using a number of biocompatible acrylic and methacrylic monomers. This offers a platform to manipulate, track and control cellular behaviour by the in cellulo generation of macromolecules that have the ability to alter cellular motility, label cells by the generation of fluorescent polymers for long-term tracking studies, as well as generate a variety of nanostructures within cells. It is remarkable that free radical polymerization chemistry can take place within such complex cellular environments. This demonstration opens up a multitude of new possibilities for how chemists can modulate cellular function and behaviour and for understanding cellular behaviour in response to the generation of free radicals.


Assuntos
Radicais Livres/química , Polimerização/efeitos da radiação , Ácidos Polimetacrílicos/síntese química , Poliestirenos/síntese química , Acrilatos/química , Acrilatos/efeitos da radiação , Acrilatos/toxicidade , Citoesqueleto de Actina/efeitos dos fármacos , Compostos de Anilina/química , Compostos de Anilina/efeitos da radiação , Compostos de Anilina/toxicidade , Movimento Celular/efeitos dos fármacos , Fluorescência , Células HeLa , Humanos , Metacrilatos/química , Metacrilatos/efeitos da radiação , Metacrilatos/toxicidade , Propano/análogos & derivados , Propano/química , Propano/efeitos da radiação , Fase S/efeitos dos fármacos , Estirenos/química , Estirenos/efeitos da radiação , Estirenos/toxicidade , Raios Ultravioleta , Compostos de Vinila/química , Compostos de Vinila/efeitos da radiação , Compostos de Vinila/toxicidade
7.
J Appl Oral Sci ; 27: e20180111, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30624464

RESUMO

OBJECTIVES: Several anti-proteolytic dentin therapies are being exhaustively studied in an attempt to reduce dentin bond degradation and improve clinical performance and longevity of adhesive restorations. This study assessed the effect of epigallocatechin-3-gallate (EGCG) on long-term bond strength when incorporated into adhesives. MATERIAL AND METHODS: Adhesive systems were formulated with EGCG concentrations of 0 wt%: (no EGCG; control); 0.5 wt% EGCG; 1.0 wt% EGCG, and 1.5 wt% EGCG. Flexural strength (FS), modulus of elasticity (ME), modulus of resilience (MR), compressive strength (CS), degree of conversion (DC), polymerization shrinkage (PS), percentage of water sorption (%WS), percentage of water solubility (%WL) and cytotoxicity properties were tested. Dentin microtensile bond strength (µTBS) was evaluated after 24 h and again after 6 months of water storage. The adhesive interface was analyzed using scanning electron microscopy (SEM). RESULTS: No significant differences were found among the groups in terms of FS, ME, MR, CS and PS. EGCG-doped adhesives increased the DC relative to the control group. EGCG concentrations of 1.0 wt% and 0.5 wt% decreased the WS of adhesives. WL decreased in all cases in which EGCG was added to adhesives, regardless of the concentration. EGCG concentrations of 1.0 wt% and 0.5 wt% reduced cytotoxicity. EGCG concentrations of 1.0 wt% and 0.5 wt% preserved µTBS after 6 months of storage, while 1.5 wt% EGCG significantly decreased µTBS. SEM: the integrity of the hybrid layer was maintained in the 0.5 wt% and 1.0 wt% EGCG groups. CONCLUSION: EGCG concentrations of 1.0 wt% and 0.5 wt% showed better biological and mechanical performance, preserved bond strength and adhesive interface, and reduced cytotoxicity.


Assuntos
Bis-Fenol A-Glicidil Metacrilato/química , Catequina/análogos & derivados , Adesivos Dentinários/química , Metacrilatos/química , Análise de Variância , Bis-Fenol A-Glicidil Metacrilato/toxicidade , Cânfora/análogos & derivados , Cânfora/química , Catequina/química , Catequina/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Força Compressiva , Dentina/química , Dentina/efeitos dos fármacos , Adesivos Dentinários/toxicidade , Módulo de Elasticidade , Fibroblastos/efeitos dos fármacos , Resistência à Flexão , Humanos , Teste de Materiais , Metacrilatos/toxicidade , Microscopia Eletrônica de Varredura , Polimerização , Valores de Referência , Reprodutibilidade dos Testes , Solubilidade , Propriedades de Superfície , Resistência à Tração , Fatores de Tempo , Água/química
8.
Clin Oral Investig ; 23(1): 133-139, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29603022

RESUMO

OBJECTIVES: Tooth-colored composites have emerged as a standard restorative material in caries therapy and have largely replaced materials such as silver amalgam or glass ionomer cements. In addition to their superior esthetics and desirable mechanical properties, composites also comprise negative characteristics, such as wear, shrinkage, and an adverse biocompatibility. Modifications of classic resin-based dental composites have been developed to overcome these shortcomings. For example, ormocers are innovative inorganic-organic hybrid polymers that form a siloxane network modified by the incorporation of organic groups. Recently, a new ormocer, Admira Fusion (VOCO), was introduced to composite technology. The absence of cytotoxic matrix monomers leads to the hypothesis that ormocers have improved biocompatibility compared to resin-based dental restorative materials. MATERIALS AND METHODS: The aim of this study was to compare the cytotoxic effects of Admira Fusion to a nanohybrid composite (GrandioSO, VOCO) and a nanofiller composite (Filtek Supreme XTE, 3M Espe) on the standard dermal mouse fibroblasts (L929) and human gingival fibroblasts (GF-1) via a Cell Counting Kit-8 (CCK-8) assay. RESULTS: Admira Fusion was significantly less cytotoxic than GrandioSO and Filtek Supreme XTE to both the standard mouse dermal fibroblasts (L929) and human gingival fibroblasts. CONCLUSIONS: Compared to other resin-based dental restorative materials, the ormocer (Admira Fusion) possesses a superior biocompatibility in vitro. Future research studies are needed to confirm our results. CLINICAL SIGNIFICANCE: Clinically, dental practitioners and their patients might benefit from Admira Fusion in terms of reduced adverse biologic reactions compared to resin-based dental restorative materials.


Assuntos
Resinas Acrílicas/toxicidade , Resinas Compostas/toxicidade , Materiais Dentários/toxicidade , Fibroblastos/efeitos dos fármacos , Cerâmicas Modificadas Organicamente/toxicidade , Poliuretanos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Gengiva/citologia , Humanos , Teste de Materiais , Metacrilatos/toxicidade , Camundongos , Siloxanas/toxicidade
9.
Oral Health Prev Dent ; 16(6): 525-532, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30511051

RESUMO

PURPOSE: To qualitatively and quantitatively compare the cytotoxic potentials of five different one-step self-etching adhesives: Prime&Bond One-Select (PB-OS), Optibond All-in-One (OB-AIO), G-Bond (GB), Clearfil Universal Bond (CUB), Single Bond Universal (SBU). MATERIALS AND METHODS: During the first stage of the study, the cytotoxic activities of the test materials were evaluated qualitatively using the direct contact method. In this method, the test materials were placed directly into a monkey kidney epithelial cell culture medium. Reaction zones which occurred in the culture medium were evaluated, in addition to the density and changes in the morphology of the cells. During the second stage, the cytotoxic potential of four different dilutions (1%, 0.1%, 0.01%, 0.001%) of the test materials on L929 rat fibroblast cells was quantitatively evaluated at three different time periods (24 h, 48 h, 72 h) with the MTT tetrazolium-based assay. RESULTS: In the first stage, a zone exceeding 1 cm was observed around or below SBU, CUB, GB and OB-AIO. In PB-OS, the zone borders were approximately 1 cm. In the second stage after the MTT assay, CUB was the most cytotoxic after 24 h, GB and SBU after 48 h, and OB-AIO after 72 h. CONCLUSION: All adhesives tested showed different degrees of cytotoxicity, which statistically significantly increased with dose. Changes were seen related to time.


Assuntos
Cimentos Dentários/toxicidade , Teste de Materiais , Ataque Ácido Dentário , Animais , Bis-Fenol A-Glicidil Metacrilato/toxicidade , Células Cultivadas , Estudos de Avaliação como Assunto , Haplorrinos , Metacrilatos/toxicidade , Ácidos Polimetacrílicos/toxicidade , Pesquisa Qualitativa , Ratos , Cimentos de Resina/toxicidade , Testes de Toxicidade/métodos
10.
Acta Biomater ; 78: 64-77, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30099197

RESUMO

The paucity of information on the biological risks of photopolymers in additive manufacturing is a major challenge for the uptake of the technology in the construction of medical devices in dentistry. In this paper, the biocompatibility of methacrylates for denture bases, splints, retainers and surgical guides were evaluated using the innovative zebrafish embryo model, which is providing a high potential for toxicity profiling of photopolymers and has high genetic similarity to humans. Toxicological data obtained confirmed gradations of toxicity influenced by ethanol treatment, exposure scenarios and extraction vehicles. In direct exposure tests, juvenile fish exposed to non-treated methacrylates in ultrapure water showed accelerated toxicity endpoints compared to fish in transparent E3 medium. Similarly, toxic extracts induced mostly acute responses (embryonic mortality) in contrast to cumulative chronic (sublethal and teratogenic effects) in direct exposure. Methacrylates composed of >60% Ethoxylated bisphenol A dimethacrylate produced a relatively lower conversion rate in FTIR spectroscopy, but were safe in zebrafish bioassays after ethanol treatment. The study affirms that biocompatibility was influenced primarily by physico-chemical characteristics of the materials, which subsequently influenced their residual monomer content before and after immersion in ethanol. Given the precautionary implications of the study, we propose a 3-tiered approach i.e. using approved materials, apposite manufacturing parameters and post-processing techniques that together guarantee optimal results for medical devices. STATEMENT OF SIGNIFICANCE: This study is timely and relevant since there is limited published literature that precisely describes the toxicological properties of additively manufactured methacrylates despite their increased popularity for medical devices. While it is generally accepted that the zebrafish excels as a model system for developmental toxicity, a further examination of its utility in this study using different protocols provides basis for its consideration and adoption at a crucial time when there is a lack of consensus regarding the most suited biological assessment methods for medical devices.


Assuntos
Odontologia , Equipamentos e Provisões , Metacrilatos/toxicidade , Testes de Toxicidade , Animais , Bioensaio , Dentaduras , Embrião não Mamífero/efeitos dos fármacos , Determinação de Ponto Final , Larva/efeitos dos fármacos , Peixe-Zebra/embriologia
11.
Biomacromolecules ; 19(7): 2759-2771, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29791802

RESUMO

We show the potential of oligo(2-ethyl-2-oxazoline) (Oxn)-shielded graft copolymers of (2-aminoethyl)-methacrylate and N-methyl-(2-aminoethyl)-methacrylate for pDNA delivery in HEK cells. For the effect of grafting density and side chain length concerning improved transfection properties through the concept of shielding to be investigated, copolymers were synthesized via the macromonomer method using a combination of cationic ring opening polymerization and reversible addition-fragmentation chain transfer polymerization to vary the degree of grafting (DG = 10 and 30%) as well as the side chain degree of polymerization (DP = 5 and 20). Investigations of the polyplex formation, in vitro flow cytometry, and confocal laser scanning microscopy measurements on the copolymer library revealed classical shielding properties of the Ox side chains, including highly reduced cytotoxicity and a partial decrease in transfection efficiency, as also reported for polyethylene glycol shielding. In terms of the transfection efficiency, the best performing copolymers (A- g-Ox5(10) and M- g-Ox5(10)) revealed equal or better performances compared to those of the corresponding homopolymers. In particular, the graft copolymers with low DG and side chain DP transfected well with over 10-fold higher IC50 values. In contrast, a DG of 30% resulted in a loss of transfection efficiency due to missing ability for endosomal release, and a side chain DP of 20 hampered the cellular uptake.


Assuntos
Etilaminas/química , Metacrilatos/química , Oxazóis/química , Transfecção/métodos , Animais , Etilaminas/toxicidade , Células HEK293 , Humanos , Metacrilatos/toxicidade , Camundongos , Oxazóis/toxicidade , Ovinos
12.
J Control Release ; 282: 140-147, 2018 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-29518467

RESUMO

The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in treating multiple blood cancers has created a need for efficient methods of ex vivo gene delivery to primary human T cells for cell engineering. Here, we synthesize and evaluate a panel of cationic polymers for gene delivery to both cultured and primary human T cells. We show that a subset of comb- and sunflower-shaped pHEMA-g-pDMAEMA polymers can mediate transfection with efficiencies up to 50% in the Jurkat human T cell line with minimal concomitant toxicity (>90% viability). We then optimize primary human T cell transfection conditions including activation time, cell density, DNA dose, culture media, and cytokine treatment. We demonstrate transfection of both CD4+ and CD8+ primary human T cells with messenger RNA and plasmid DNA at efficiencies up to 25 and 18%, respectively, with similarly high viability.


Assuntos
DNA/administração & dosagem , Portadores de Fármacos/química , Metacrilatos/química , Nylons/química , Poli-Hidroxietil Metacrilato/química , RNA Mensageiro/administração & dosagem , Linfócitos T/metabolismo , Transfecção/métodos , Sobrevivência Celular/efeitos dos fármacos , DNA/genética , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Humanos , Células Jurkat , Metacrilatos/metabolismo , Metacrilatos/toxicidade , Nylons/metabolismo , Nylons/toxicidade , Plasmídeos/administração & dosagem , Plasmídeos/genética , Poli-Hidroxietil Metacrilato/metabolismo , Poli-Hidroxietil Metacrilato/toxicidade , RNA Mensageiro/genética , Linfócitos T/efeitos dos fármacos
13.
Toxicol In Vitro ; 47: 8-17, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29107684

RESUMO

Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.


Assuntos
Apoptose/efeitos dos fármacos , Reagentes para Ligações Cruzadas/toxicidade , Reparo do DNA/efeitos dos fármacos , Etilenoglicóis/toxicidade , Gengiva/efeitos dos fármacos , Metacrilatos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaio Cometa , Dano ao DNA , Materiais Dentários/toxicidade , Indução Enzimática/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Gengiva/citologia , Gengiva/metabolismo , Glutationa Peroxidase/química , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Concentração Osmolar , Plasmídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/química , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
14.
Regul Toxicol Pharmacol ; 92: 104-127, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29180022

RESUMO

Categories and read-across are essential tools for supplying information for assessments of endpoints without data while minimizing animal testing. This study is based on the guidance of ECHA in its Read-Across Framework (RAAF). A category of C1 - C8 alkyl methacrylate esters (methyl, ethyl, n-butyl, iso-butyl and 2-ethylhexyl) was constructed to fill in missing information for human health endpoints using read-across as a permitted adaptation under EU REACH. The esters form a series with common functional groups, small incremental changes of electrophilicity by molecular weight, and rapid hydrolysis by ester cleavage. Read-across is justified by two common specific modes of action, direct electrophilic reaction of the parent compounds and the potential inherent toxicities of the common metabolites methacrylic acid and the corresponding alcohols. The toxicological profile is very similar for all category members and not driven by the alcohol metabolites. Data gaps can be filled in with high confidence based on the number of studies available, the effects therein observed and the toxicological profiles of the hydrolysis products. The guidance provided by the RAAF enabled data gaps to be filled in a robust manner.


Assuntos
Ésteres/toxicidade , Metacrilatos/toxicidade , Álcoois/toxicidade , Animais , Substâncias Perigosas/toxicidade , Humanos , Coelhos , Ratos , Medição de Risco
16.
J Contemp Dent Pract ; 18(9): 771-774, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28874639

RESUMO

AIM: Different biomaterials and techniques have been introduced in the field of prosthetic dentistry with the purpose of replacement and rehabilitation of the edentulous areas. Due to their shorter setting time, the light-activated restorative and prosthetic materials have the capability of releasing few amount of cytotoxic materials in the oral cavity. Polymer materials [urethane dimethacrylate (UDMA) and bis-acryl] are assumed to have high mechanical properties. Polymethyl methacrylate (PMMA) offers numerous advantages of being highly esthetic in nature and at the same time being cost-effective. Hence, this study aimed to assess and compare the water sorption and cytotoxicity of light-activated UDMA denture base resin and conventional heat-activated PMMA resin. MATERIALS AND METHODS: This study included assessment and comparison of water sorption and cytotoxicity of heat-activated PMMA resin and light-activated UDMA denture base system. Fabrication of heat-activated PMMA resin and UDMA specimens was done by investing the wax patterns in stone molds using manufacturer's instructions. Contraction of the specimens was done for assessment of cytotoxicity and water resorption of the UDMA and PMMA resin samples. All the results were analyzed by Statistical Package for the Social Sciences software version 18.0. Chi-square test and one-way analysis of variance tests were used for the assessment of the level of significance; p < 0.05 was taken as significant. RESULTS: Mean lysis score observed in the PMMA and UDMA groups was 0.4 and 0.3 respectively. While observing at the 3 months time, the mean water resorption in the PMMA and UDMA groups was found to be 37.9 and 40.2 respectively. Significant difference in relation to water resorption was observed between the two study groups only at 3 months time. CONCLUSION: Both materials used in this study are nontoxic. Furthermore, UDMA resin materials exhibited lower water resorption after more than 1 month of time of storage. CLINICAL SIGNIFICANCE: Water resorption is similar for different denture base resin systems till 1 months time.


Assuntos
Materiais Dentários/química , Materiais Dentários/toxicidade , Bases de Dentadura , Metacrilatos/química , Metacrilatos/toxicidade , Polimetil Metacrilato/química , Polimetil Metacrilato/toxicidade , Poliuretanos/química , Poliuretanos/toxicidade , Água/química , Adsorção , Técnicas In Vitro , Teste de Materiais
17.
J Dent ; 65: 76-82, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28711338

RESUMO

OBJECTIVES: Dental resin-based materials are widely used in modern dentistry. Especially, resin cements enjoy great popularity and are utilized in many applications. Nevertheless, monomers could be released from the resinous matrix, thus interact with surrounding tissues, cause adverse biological reactions and may lead in cases of implant retained restorations to peri-implant bone destruction. Hence, we performed an in-vitro study to determine cytotoxicity of resin monomers on osteoblast-like cells. METHODS: Three permanent osteoblast-like cell lines from tumor origin (MG-63 and Saos-2) as well as immortalized human fetal osteoblasts (hFOB 1.19) were used and treated with different concentrations of the main monomers: BisGMA, UDMA, TEGDMA and HEMA. The impact on cell viability was monitored using three different cytotoxicity tests: alamarBlue, XTT, and LDH assay. Mean±SEM were calculated and statistical analysis was performed with GraphPad Prism software. RESULTS: All monomers tested caused concentration dependent cytotoxic effects on the three investigated osteoblast-like cell lines. Although all three cell viability assays showed comparable results in cytotoxic ranking of the monomers (BisGMA > UDMA > TEGDMA > HEMA), higher differences in the absolute values were detected by the various test methods In addition, also a cell line dependent influence on cell viability could be identified with higher impact on the immortalized hFOB 1.19 cells compared to both osteosarcoma cell lines (MG-63, Saos-2). CONCLUSIONS: Monomer concentrations detected in elution studies caused toxic effects in osteoblast-like cells. Although the results from in-vitro studies cannot be directly transferred to a clinical situation our results indicate that released monomers from composite resin cements may cause adverse biological effects and thereby possibly lead to conditions favoring peri-implantitis and bone destruction. CLINICAL SIGNIFICANCE: The wide use of composite resin cements especially in implant-prosthetic treatments should be scrutinized to avoid possible clinical implications between eluted resin monomers and bone cells leading to conditions favoring peri-implantitis and bone destruction.


Assuntos
Materiais Dentários/toxicidade , Teste de Materiais , Osteoblastos/efeitos dos fármacos , Cimentos de Resina/toxicidade , Resinas Sintéticas/toxicidade , Linhagem Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Metacrilatos/toxicidade , Polietilenoglicóis/toxicidade , Ácidos Polimetacrílicos/toxicidade , Poliuretanos/toxicidade , Fatores de Tempo
18.
Macromol Biosci ; 17(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28714224

RESUMO

Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells.


Assuntos
Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Hidroxibutiratos/química , Metacrilatos/química , Neoplasias/tratamento farmacológico , Nylons/química , Paclitaxel/uso terapêutico , Poliésteres/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Tensoativos/química , Cátions/química , DNA/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Hidroxibutiratos/síntese química , Hidroxibutiratos/toxicidade , Metacrilatos/síntese química , Metacrilatos/toxicidade , Neoplasias/patologia , Nylons/síntese química , Nylons/toxicidade , Paclitaxel/farmacologia , Plasmídeos/metabolismo , Poliésteres/síntese química , Poliésteres/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transfecção
19.
J Biomater Sci Polym Ed ; 28(16): 1874-1887, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28693380

RESUMO

To improve the bioavailability of ibuprofen (IBU), we developed a novel binary complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU-PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS). The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent evaporation method and radical polymerization, respectively. The final OIDDS was obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH 7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied by laser granularity analyzer and transmission electron microscope (TEM). The inner structures of the pH-sensitive hydrogel chips were observed with an S-4800 scanning electron microscope (SEM). The distribution states of IBU in the OIDDS were also studied with X-ray diffraction (XRD) and differential scanning calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round shape with an average diameter about 100 nm. Fourier transform infrared spectrum (FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture showed that the final hydrogel had 3D net-work structures. Moreover, the poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC curves suggested that IBU distributed in the OIDDS with an amorphous state. The cumulated release profiles indicated that the final OIDDS could release IBU in alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore, the novel OIDDS could improve the oral bioavailability of IBU, and had a potential application in drug delivery.


Assuntos
Ibuprofeno/administração & dosagem , Ibuprofeno/química , Ácido Láctico/química , Metacrilatos/administração & dosagem , Metacrilatos/química , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Ácido Poliglicólico/química , Células 3T3 , Administração Oral , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Ibuprofeno/toxicidade , Metacrilatos/toxicidade , Camundongos , Polietilenoglicóis/toxicidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
20.
Adv Clin Exp Med ; 26(1): 15-22, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28397427

RESUMO

BACKGROUND: The problem of effective treatment of dentin hypersensitivity is still valid and not fully resolved. OBJECTIVES: The aim of the study was to evaluate the potential toxicity against body tissues of an experimental preparation which is supposed to reduce dentin hypersensitivity and to compare it to a commercial formulation Seal & Protect (Dentsply) by means of measuring the activity of mitochondrial dehydrogenases (the MTT assay). MATERIAL AND METHODS: The study used an original protective formulation which is supposed to eliminate hypersensitivity of dentin. A commercial preparation Seal & Protect (Dentsply) was used as the comparative material. Cytotoxic activity of the tested preparations (experimental and commercial) on murine lymphocyte cells CCL-1™ (NCTC clone 929) was determined in indirect contact with the use of the MTT test that measured the activity of the mitochondrial dehydrogenase enzyme. RESULTS: A comparison of the results obtained in the MTT assay for the commercial preparation Seal & Protect (Dentsply) and the experimental formulation indicates that an experimental formulation has considerably lower cytotoxicity before polymerization, when compared to the commercial formulation, regardless of its dilution. However, after the polymerization of the commercial formulation was completed, its parameters improved significantly, especially for higher dilution values (1 : 10 and 1 : 15). Results for the experimental formulation are higher, particularly for the dilution value of 1 : 5. The overall summary of the results obtained from the MTT assay for the commercial preparation Seal & Protect (Dentsply) and the experimental formulation indicates that the experimental formulation had a significantly lower cytotoxicity before polymerization in comparison with the commercial formulation, regardless of dilution. CONCLUSIONS: Estimating the biocompatibility of a given material is not simple, and measurement methods are rapidly evolving, as more and more is known about the interaction between dental materials and oral tissues, and also as a result of improvements in testing techniques.


Assuntos
Materiais Dentários/toxicidade , Sensibilidade da Dentina/prevenção & controle , Linfócitos/efeitos dos fármacos , Metacrilatos/toxicidade , Animais , Teste de Materiais , Camundongos , Polimerização , Polimetil Metacrilato/toxicidade
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