RESUMEN

Background: Considering the variability of finishing protocols for composite resins, the literature does not offer a consensus about the influence of these approaches to obtain a final polishing and whether the physical properties of these composite resins change at different analysis times. Therefore, the study analyzed the microhardness, roughness, color stability, and gloss of a nanocomposite resin with different finishing, aging with coffee, and repolishing protocols. Material and Methods: Nanocomposite resin samples were divided into three finishing protocol groups: Diamond burs (F and FF), multi-fluted tungsten carbide burs (18 and 30 flutes), and coarse and medium abrasive discs (Soflex-3M). All protocols used spiral rubber tips (F and FF) for polishing. Knoop microhardness (KHN), roughness (Ra), color changes (ΔE00 and YI), and gloss (GU) were analyzed. Scanning electron microscopy provided images of resins and finishing and polishing instruments. Results: Resin KHN (p<0.001) decreased, and Ra (p<0.001), ΔE00 (p<0.001), and YI (p<0.001) increased after aging with coffee, regardless of finishing protocol. Abrasive discs showed lower color changes, YI, and Ra and higher GU. Repolishing restored KHN and Ra but not ΔE00 (p>0.05) and YI (p>0.05). Conclusions: Abrasive disc finishing reduced roughness and yellowness and increased nanocomposite resin gloss after aging with coffee. Key words:Color, Composite resins, Dental materials, Staining, Surface properties.

RESUMEN

OBJECTIVES: To assess color change efficacy and the adverse effects of varied over-the-counter (OTC) bleaching protocols. METHODOLOGY: The study included randomized clinical trials evaluating color changes from OTC bleaching agents. Nine databases were searched, including the partial capture of the grey literature. The RoB2 tool analyzed the individual risk of bias in the studies. Frequentist network meta-analyses compared treatments through common comparators (∆Eab* and ∆SGU color changes, and tooth sensitivity), integrating direct and indirect estimates and using the mean and risk differences as effect measures with respective 95% confidence intervals. The GRADE approach assessed the certainty of the evidence. RESULTS: Overall, 37 remaining studies constituted the qualitative analysis, and ten composed the meta-analyses. The total sample included 1,932 individuals. ∆Eab* was significantly higher in groups 6% hydrogen peroxide (HP) strips (≥ 14 h). ∆SGU was significantly higher in groups at-home 10% carbamide peroxide (CP) (≥ 14 h), followed by 6% HP strips (≥ 14 h) and 3% HP strips (≥ 14 h). At-home 10% CP (7-13 h) and placebo showed lower risks of tooth sensitivity without significant differences between these treatments. CONCLUSION: Considering the low level of evidence, OTC products presented satisfactory short-term effects on tooth bleaching compared to the placebo, with little to no impact on dentin hypersensitivity and gingival irritation. CLINICAL RELEVANCE: OTC products are proving to be practical alternatives for tooth whitening. However, patients should be advised about the possible risks of carrying out such procedures without professional supervision.

Asunto(s)

Sensibilidad de la Dentina , Blanqueadores Dentales , Blanqueamiento de Dientes , Humanos , Peróxido de Carbamida , Color , Sensibilidad de la Dentina/tratamiento farmacológico , Peróxido de Hidrógeno , Ácido Hipocloroso , Metaanálisis en Red , Medicamentos sin Prescripción/efectos adversos , Peróxidos , Blanqueamiento de Dientes/efectos adversos , Blanqueamiento de Dientes/métodos , Blanqueadores Dentales/efectos adversos , Blanqueadores Dentales/farmacología , Urea

RESUMEN

Sodium butyrate-loaded nanoparticles coated chitosan (NaBu-loaded nanoparticles/CS) were developed to treat the choroidal neovascularization in wet age-related macular degeneration (AMD). The nanoparticles were produced by double emulsification and solvent evaporation technique, optimized by experimental statistical design, characterized by analytical methods, investigated in terms of in vitro and in vivo ocular biocompatibility, and evaluated as an antiangiogenic system in vivo. The NaBu-loaded nanoparticles/CS were 311.1 ± 3.1 nm in diameter with a 0.208 ± 0.007 polydispersity index; had a +56.3 ± 2.6 mV zeta potential; showed a 92.3 % NaBu encapsulation efficiency; and sustained the drug release over 35 days. The NaBu-loaded nanoparticles/CS showed no toxicity to human retinal pigment epithelium cells (ARPE-19 cells); was not irritant to the chorioallantoic membrane (CAM); did not interfere in the integrity of the retinal layers of rat's eyes, as detected by the Optical Coherence Tomography and histopathology; and inhibited the angiogenesis in CAM assay. The NaBu-loaded nanoparticles/CS could be a therapeutic alternative to limit the neovascularization in AMD.

Asunto(s)

Quitosano , Nanopartículas , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Ácido Butírico/uso terapéutico , Humanos , Ratas , Solventes , Degeneración Macular Húmeda/tratamiento farmacológico

RESUMEN

Aim: The development of postoperative pain following root canal instrumentation may impair patient's comfort and undermine their trust in the dentist. This study assessed the effect of root canal instrumentation techniques (rotary (PTN; ProTaper Next®) and reciprocating (R; Reciproc®)) on the postoperative pain intensity (primary outcome) and tenderness on biting (secondary outcome) of patients' asymptomatic molars. Methodology: This study protocol was registered with ReBec-WHO (U1111-1182-2800). From a pool of 112 patients evaluated for eligibility (healthy adults (≤18 years old)), with a single asymptomatic molar (maxillary or mandibular) indicated for root canal treatment, diagnosed with asymptomatic irreversible pulpitis (including chronic hyperplastic pulpitis), 75 were randomly allocated in similar proportions to receive the intervention (two-appointment root canal therapy) in either the PTN or R group. The allocated procedures were performed using standardized protocols. Participants (blinded to the instrumentation technique) rated their pain intensity at 6, 12 and 24 h and from day 2 to day 7 following the root canal instrumentation appointment using a VAS and an NRS; the ibuprofen tablets taken and the presence of tenderness on biting were recorded. The instrumentation time was registered. Univariate and multivariate statistics measured the effect of independent variables on the outcomes. Results: From the 75 patients allocated, 8 patients (4 from each group) were lost; in total, 33 patients were analyzed in the PTN group and 34 in the R group. The frequencies of postoperative pain (p > 0.05) and tenderness on biting (p > 0.05) were similar between groups. The medication intake (mean of 1.31 tablets) and the time of instrumentation (approximately 11 min) were similar between groups. Conclusion: ProTaper Next and Reciproc® caused a slight risk of tenderness on biting and contributed to similar self-reported postoperative pain (low intensity) up to 7 days following root canal shaping.

RESUMEN

The advantage of using an Enamel matrix derivative EMD Emdogain as an intracanal medication could be a manner to strength the tooth structure, improving the physical and chemical properties of dentin. We tested, in vitro, the effect of Emdogain on the surface microhardness and chemical composition of root dentin. Ten human teeth were used to produce dentin specimens originated from the canal walls (n = 30) that remained in contact to Emdogain gel for 90 days. Baseline and 90-days after Emdogain treatment measurements were performed using Fourier Transform Infrared Spectroscopy (ATR/FTIR), Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS) and Knoop indenters. The use of EMD (Emdogain) for 90 days in contact with human root canal dentin specimens did not alter the microhardness and morphology of dentin. The elemental structure of dentin was altered because there was a reduction in carbonate content.

Asunto(s)

Blanqueamiento de Dientes , Diente , Dentina/química , Dureza , Humanos , Microscopía Electrónica de Rastreo , Blanqueamiento de Dientes/métodos

RESUMEN

OBJECTIVE: This laboratory randomized study was designed to evaluate the effect of polishing on roughness and color stability of bleached teeth after coffee immersion. MATERIALS AND METHODS: Ninety bovine crowns were randomly allocated to six groups (n = 15), according to bleaching protocols: At-home: standard protocol using 10% hydrogen peroxide (HP) or In-office: standard protocol using 35% HP; and with polishing protocols: (1) no polishing, (2) bleached enamel polished with #0.5 µm or (3) #2-4 µm diamond particles grit pastes. Samples were daily immersed into coffee solution for 45 min followed by mechanical brushing simulation (30 s) for 30 days. The surface roughness (Ra) and color alteration, expressed by ΔEab , ΔE00 , and whitening index (WI) were analyzed at baseline, after bleaching/polishing protocols and after coffee solution staining. The surface from each group was examined using a scanning electron microscope. Data were analyzed by two-way repeated measure analysis of variance followed by the Tukey test (α = 0.05). RESULTS: Staining increases Ra, ΔEab , ΔE00 , and decreases WI values. Polishing after bleaching did not prevent staining, however, tooth polished with #0.5 µ-grit polishing paste showed better performance than #2-4 µ-grit (ΔEab : p = 0.001/ΔE00 : p = 0.003). Scanning electron microscope revealed a more irregular surface after coffee staining for all groups regardless bleaching/polishing protocols. CONCLUSIONS: Using #0.5 µ-grit diamond paste to polish 35%HP in-office bleached enamel reduces the roughness and tooth staining. However, polishing after 10%HP at-home bleached enamel neither affects roughness nor improves tooth color stability after exposure to coffee. CLINICAL SIGNIFICANCE: Polishing after at-home bleaching does not have benefits but after 35% hydrogen peroxide in-office bleaching, the polishing with #0.5 µ-grit polishing paste is indicated to reduce roughness and the tooth staining over time.

Asunto(s)

Blanqueadores Dentales , Blanqueamiento de Dientes , Animales , Bovinos , Café , Color , Esmalte Dental , Peróxido de Hidrógeno , Polonia , Propiedades de Superficie , Blanqueamiento de Dientes/métodos

RESUMEN

AIM: To analyse the discolouration, radiopacity, pH and calcium ion release of Biodentine (BD), Bio-C repair (BCR) and Bio-C temp (BCT), as well as their biological effects on human dental pulp cells (hDPCs). METHODOLOGY: Sixty-four extracted bovine incisors were prepared to simulate crown fractures with pulp exposure and open root apex. The roots were filled using a mixture of agar and blood (control), and BD, BCR or BCT were placed over this mixture. Colour assessment analyses of the samples were performed before and immediately after material insertion and repeated at 30 and 90 days, using a spectrophotometer. The colour change of each specimen was evaluated at the crown and calculated based on the CIELab colour space. Digital radiographs were acquired for radiopacity analysis. hDPCs were placed in contact with different dilutions of culture media previously exposed to such materials and tested for cell viability using the MTT assay. The pH and calcium ion release of all materials were measured after 24 h; the data were assessed using one-way analysis of variance (ANOVA). Cell viability was analysed by two-way ANOVA. Differences in colour parameters and wound-healing data were assessed by two-way repeated measures ANOVA (α = 0.05). Tukey's and Dunnett's tests were used to compare the experimental groups with the control group. RESULTS: BCR had grater radiopacity and smaller colour alteration (ΔEab/ΔE00) than the other materials tested (p < .005; p < .001). No significant differences in pH were found amongst the tested materials (p > .05). BCT was associated with the largest release of calcium ions (p < .0001). BD had cell viability similar to that of the control at the lowest dilutions, and BCR was similar to that of the control, regardless of the dilution tested (p > .05). BCT had a lower percentage of viability than that of the control at all tested dilutions (p < .0001). Cell migration rates in BD and BCR were similar to those in the control group after 24 h and 48 h (p > .05), whilst BCT had larger voids than the control in both periods (p < .0001). CONCLUSIONS: BCR, BCT and BD were associated with tooth discolouration. BCR had the lowest staining values, the highest radiopacity and viability greater than 80% hDPCs.

Asunto(s)

Materiales de Obturación del Conducto Radicular , Decoloración de Dientes , Animales , Compuestos de Calcio , Bovinos , Supervivencia Celular , Humanos , Pulpotomía , Silicatos

RESUMEN

This systematic review assessed the effectiveness of ozone (O3) in the color change of in-office tooth bleaching in vital teeth (TB) and the sensitivity control. Only randomized controlled clinical trials were included. Seven databases were used as primary search sources, and three additional sources were searched to capture the "grey literature" partially. The JBI tool was used to assess the risk of bias. TB was assessed using the ΔELab color change metric comparing tooth color pre- and post-bleaching. We meta-analyzed the ΔELab estimates per method and calculated the absolute standardized mean difference using random-effect models. The GRADE approach assessed the certainty of the evidence. The ΔELab estimates ranged from 1.28 when the O3 was used alone to 6.93 when combined with hydrogen peroxide (HP). Two studies compared O3 and HP alone, but their TB was similar (SMD = - 0.02; 95%CI: - 0.54; 0.49). The bleaching effectiveness for the combination of O3 + HP compared to HP was similar (SMD = 0.38; 95%CI: - 0.04; 0.81). Thus, based on the available literature, our findings suggest that O3 is not superior to the conventional technique using HP on the change of tooth color. The O3 did not present sensitivity when used alone. When O3 was used in combination with HP, patients reported hypersensitivity only when O3 was applied before HP, i.e., no sensitivity was perceived when O3 was applied after HP.

Asunto(s)

Sensibilidad de la Dentina/inducido químicamente , Ozono/farmacología , Blanqueadores Dentales/farmacología , Blanqueamiento de Dientes/métodos , Colorimetría , Interacciones Farmacológicas , Humanos , Peróxido de Hidrógeno/administración & dosificación , Peróxido de Hidrógeno/efectos adversos , Peróxido de Hidrógeno/farmacología , Ozono/administración & dosificación , Ozono/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Blanqueamiento de Dientes/efectos adversos , Blanqueadores Dentales/administración & dosificación , Blanqueadores Dentales/efectos adversos

RESUMEN

Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCM-DMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.

Asunto(s)

Endoftalmitis/tratamiento farmacológico , Polietileneimina/análogos & derivados , Vancomicina/farmacología , Antibacterianos/farmacología , Línea Celular , Portadores de Fármacos , Liberación de Fármacos , Ojo/efectos de los fármacos , Humanos , Ácido Hialurónico/metabolismo , Ácido Hialurónico/farmacología , Nanopartículas , Tamaño de la Partícula , Polietileneimina/química , Polietileneimina/farmacología , Vancomicina/química

RESUMEN

The aim of this retrospective study was to evaluate the survival and associated factors for the longevity of direct posterior restorations and to verify whether the geographic location of public health units could influence the long-term survival of such restorations. Data were extracted from electronic patient files of the Brazilian public oral health services. The sample comprised 2,405 class I and II restorations performed 4 to 24 years ago (mean, 8.9 years) in 351 patients (6.8 teeth/patient) across 12 public health units located in different city regions (42 professionals-55 restorations). The restoration was considered successful if it had not been repaired or replaced at the time of evaluation; failure was defined as replacement of the restoration, the need for endodontic treatment, tooth/restoration fracture or tooth extraction. Data were analyzed using the Kaplan-Meier test for restoration survival and Cox regression to evaluate the factors associated with failure. The majority of the restorations involved the use of amalgam (85%), involved a single face (70%), and were without pulp/dentin capping (85%). The overall survival rate was 95%, and the mean observation time was 8.9 years. The restoration survival was 79% (95% CI: 60.6-89.5) over 24 years, and the mean survival time was 22.2 years (95% CI: 21.9-22.6 years). The annual failure rate up to 24 years was 0.9%. After the adjustment, only the number of restored faces and the geographic location where the restoration was performed remained associated with failure of the restoration. The direct posterior restorations performed at the evaluated public health service units presented high survival rates. The restorations of people with lower access to POHS had lower survival rates. Class I restorations presented higher survival rates than class II restorations with two or more faces, regardless of the restorative material used.

Asunto(s)

Fracaso de la Restauración Dental , Restauración Dental Permanente , Brasil , Femenino , Humanos , Masculino , Salud Bucal , Estudios Retrospectivos

RESUMEN

The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to­lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 µM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV-vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.

Asunto(s)

Alcaloides/química , Antimaláricos/farmacología , Mutágenos/farmacología , Permeabilidad/efectos de los fármacos , Piridinas/química , Tiazoles/química , Animales , Células CACO-2 , Línea Celular , Línea Celular Tumoral , Cloroquina/farmacología , Femenino , Hemoproteínas/química , Humanos , Malaria/tratamiento farmacológico , Ratones , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos

RESUMEN

Vulvovaginal candidiasis is an inflammation localized in the vulvovaginal area. It is mostly caused by Candida albicans. Its treatment is based on the systemic and local administration of antifungal drugs. However, this conventional therapy can fail owing to the resistance of the Candida species and noncompliance of patients. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers are single-use, antifungal, controlled drug delivery systems, and represent an alternative therapeutic scheme for the local treatment of vulvovaginal candidiasis. Nanofibers were characterized by analytical techniques and with an in vitro drug delivery study. In vitro and in vivo fungicidal activity of amphotericin B released from nanofibers was evaluated using the agar diffusion method and an experimental murine model of vulvovaginal candidiasis, respectively. Analytical techniques showed that amphotericin B was physically mixed in the polymeric nanofibers. Nanofibers controlled the delivery of therapeutic doses of amphotericin B for 8 consecutive days, providing effective in vitro antifungal activity and eliminated the in vivo vaginal fungal burden after 3 days of treatment and with only one local application. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers could be potentially applied as an alternative strategy for the local treatment of vulvovaginal candidiasis without inducing fungal resistance, yet ensuring patient compliance.

Asunto(s)

Anfotericina B/química , Anfotericina B/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Candidiasis Vulvovaginal/tratamiento farmacológico , Nanofibras/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Animales , Candida/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Femenino , Pruebas de Sensibilidad Microbiana/métodos , Ratas , Ratas Wistar

RESUMEN

Etoposide-loaded poly(lactic-co-glycolic acid) implants were developed for intravitreal application. Implants were prepared by a solvent-casting method and characterized in terms of content uniformity, morphology, drug-polymer interaction, stability, and sterility. In vitro drug release was investigated and the implant degradation was monitored by the percent of mass loss. Implants were inserted into the vitreous cavity of rabbits' eye and the in vivo etoposide release profile was determined. Clinical examination and the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method were performed to evaluate the implant tolerance. The original chemical structure of the etoposide was preserved after incorporation in the polymeric matrix, which the drug was dispersed uniformly. In vitro, implants promoted sustained release of the drug and approximately 57% of the etoposide was released in 50 days. In vivo, devices released approximately 63% of the loaded drug in 42 days. Ophthalmic examination and HET-CAM assay revealed no evidence of toxic effects of implants. These results tend to show that etoposide-loaded implants could be potentially useful as an intraocular etoposide delivery system in the future.

Asunto(s)

Implantes de Medicamentos/metabolismo , Etopósido/metabolismo , Ácido Láctico/metabolismo , Ácido Poliglicólico/metabolismo , Cuerpo Vítreo/metabolismo , Animales , Pollos , Implantes de Medicamentos/administración & dosificación , Implantes de Medicamentos/química , Etopósido/administración & dosificación , Etopósido/química , Inyecciones Intravítreas , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Masculino , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos , Cuerpo Vítreo/efectos de los fármacos

RESUMEN

BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1ß, TNF-α, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.

Asunto(s)

Clindamicina/administración & dosificación , Clindamicina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Retina/efectos de los fármacos , Animales , Materiales Biocompatibles/química , Línea Celular , Sistemas de Liberación de Medicamentos/métodos , Células Ependimogliales , Femenino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Inyecciones Intravítreas/métodos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Prótesis e Implantes , Ratas , Ratas Endogámicas Lew , Retina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Cuerpo Vítreo/efectos de los fármacos , Cuerpo Vítreo/metabolismo

RESUMEN

In this study, the methotrexate (MTX) was incorporated into the poly(ε-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-α and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile.

Asunto(s)

Inhibidores de la Angiogénesis/administración & dosificación , Antiinflamatorios/administración & dosificación , Preparaciones de Acción Retardada/química , Metotrexato/administración & dosificación , Poliésteres/química , Inhibidores de la Angiogénesis/farmacología , Animales , Antiinflamatorios/farmacología , Colágeno/análisis , Citocinas/análisis , Sistemas de Liberación de Medicamentos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Neovascularización Patológica/tratamiento farmacológico , Prótesis e Implantes

RESUMEN

PURPOSE: To develop thalidomide-loaded poly-lactide-co-glycolide implants and evaluate its in vivo release and biological activity against inflammation and angiogenesis after subcutaneous administration. METHODS: Implants were prepared by the hot molding technique and characterized using stereomicroscopy, thermal analysis and X-ray diffraction. Swiss mice, divided in groups 1-3, received a subcutaneous implant containing 25% (w/w), 50% (w/w) or 75% (w/w) of thalidomide, respectively (n=6). The drug levels were determined during a 28-day study period. The toxicity associated with the implants was evaluated by light microscopy. The potential of the developed implant in the inhibition of inflammation and angiogenesis was evaluated in vivo using the sponge model. RESULTS: Thalidomide implant was developed and its characterization proved the stability of the drug and the polymer during preparation. Release profiles in vivo demonstrated an extended release of thalidomide from the implants during the 28 days. Histological evaluation did not show any sign of intense local inflammatory response to the presence of the implants in the subcutaneous pouch. The thalidomide implant reduced the number of vessels and N-acetyl-b-glucosaminidase (NAG) in vivo. CONCLUSION: The biodegradable implants delivered safe doses of thalidomide that were also effective to induce angiogenesis and inflammation regression.

Asunto(s)

Materiales Biocompatibles/química , Inflamación/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Talidomida/administración & dosificación , Talidomida/uso terapéutico , Acetilglucosaminidasa/metabolismo , Animales , Rastreo Diferencial de Calorimetría , Modelos Animales de Enfermedad , Femenino , Hemoglobinas/metabolismo , Inflamación/patología , Inyecciones Subcutáneas , Ácido Láctico/química , Ratones , Neovascularización Patológica/patología , Peroxidasa/metabolismo , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Piel/efectos de los fármacos , Piel/patología , Talidomida/farmacología , Difracción de Rayos X

RESUMEN

The aim of this study was to evaluate the microtensile bond strength (µTBS) of two substrates (enamel and dentin) considering two study factors: type of composite resin [methacrylate-based (Filtek Supreme) or silorane-based (Filtek LS)] and aging time (24 h or 3 months). Twenty human molars were selected and divided into 2 groups (n=10) considering two dental substrates, enamel or dentin. The enamel and dentin of each tooth was divided into two halves separated by a glass plate. Each tooth was restored using both tested composite resins following the manufacturer's instructions. The samples were sectioned, producing 4 sticks for each composite resin. Half of them were tested after 24 h and half after 3 months. µTBS testing was carried out at 0.05 mm/s. Data were analyzed by three-way ANOVA and Tukey's HSD tests at α=0.05. Significant differences between composite resins and substrates were found (p<0.05), but no statistically significant difference was found for aging time and interactions among study factors. The methacrylate-based resin showed higher µTBS than the silorane-based resin. The µTBS for enamel was significantly higher than for dentin, irrespective of the composite resin and storage time. Three months of storage was not sufficient time to cause degradation of the bonding interaction of either of the composite resins to enamel and dentin.

Asunto(s)

Esmalte Dental , Dentina , Metacrilatos , Resinas de Silorano , Resistencia a la Tracción , Humanos , Técnicas In Vitro

RESUMEN

PURPOSE: Tacrolimus is a potent immunosuppressive agent with limited corneal penetration. Microemulsions can increase the drug solubility and enhance drug absorption in the eye. This work aimed to develop a tacrolimus microemulsion as well as to characterize and to evaluate its ocular tolerance and pharmacokinetics after topical application in rabbits. METHODS: The microemulsion was prepared by the titration with the cosurfactant technique and its physical-chemical parameters and stability were determined. The cytotoxicity was evaluated using the corneal epithelium and conjunctiva cell lines. The ocular pharmacokinetic parameters in rabbits were determined and compared with that obtained after instillation of tacrolimus suspension. RESULTS: The microemulsion containing tacrolimus was successfully developed. It was nonirritating to rabbits' eyes and it was also not toxic to the corneal and conjunctival cells. When compared to the suspension, the microemulsion containing tacrolimus presented higher values of AUC (2,912.5±245.4 min.ng/mL vs. 1,669.8±93 min.ng/mL) and Cmax (26.8±2.3 ng/mL vs. 20.7±2.8 ng/mL). On the other hand, the Cl/F value was smaller when compared to the suspension that may decrease the number of applications of eye drops. CONCLUSION: The developed microemulsion could be an alternative to reduce the systemic adverse effects of tacrolimus and, consequently, increase the patient compliance to the treatment.

Asunto(s)

Conjuntiva/metabolismo , Córnea/metabolismo , Inmunosupresores/administración & dosificación , Tacrolimus/administración & dosificación , Administración Oftálmica , Animales , Área Bajo la Curva , Línea Celular , Estabilidad de Medicamentos , Emulsiones , Femenino , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/toxicidad , Tamaño de la Partícula , Conejos , Suspensiones , Tacrolimus/farmacocinética , Tacrolimus/toxicidad

RESUMEN

CONTEXT: Methotrexate (MTX) is used in the treatment of malignancies; however, its clinical application is limited by its toxic dose-related side effects. An alternative to overcome the toxicity of the MTX in healthy tissues is the design of an implantable device capable of controlling the delivery of this drug for an extended period within the tumor site. OBJECTIVE: To develop methotrexate-loaded poly(ε-caprolactone) implants (MTX PCL implants) and to demonstrate their efficacy as local drug delivery systems capable of inhibiting Ehrlich solid tumor bearing mice. MATERIALS AND METHODS: MTX PCL implants were produced by the melt-molding technique and were characterized by FTIR, WAXS, DSC and SEM. The in vitro and in vivo release of MTX from the PCL implants was also evaluated. The efficacy of implants in inhibiting tumor cells in culture and the solid tumor in a murine model was revealed. RESULTS AND DISCUSSION: The chemical and morphological integrity of the drug was preserved into the polymeric matrix. The in vitro and in vivo release processes of the MTX from the PCL implants were modulated by diffusion. MTX diffused from the implants revealed an antiproliferative effect on tumor cells. Finally, MTX controlled and sustained released from the polymeric implants efficiently reduced 42.7% of the solid tumor in mice paw. CONCLUSION: These implantable devices represented a contribution to improve the efficacy and safety of chemotherapy treatments, promoting long-term local drug accumulation in the targeted site.

Asunto(s)

Carcinoma de Ehrlich/tratamiento farmacológico , Metotrexato/administración & dosificación , Poliésteres/administración & dosificación , Animales , Carcinoma de Ehrlich/patología , Implantes de Medicamentos , Femenino , Células HeLa , Humanos , Metotrexato/química , Ratones , Poliésteres/química , Resultado del Tratamiento , Difracción de Rayos X

RESUMEN

Poly(ε-caprolactone) implants containing etoposide, an important chemotherapeutic agent and topoisomerase II inhibitor, were fabricated by a melt method and characterized in terms of content uniformity, morphology, drug physical state, and sterility. In vitro and in vivo drug release from the implants was also evaluated. The cytotoxic activity of implants against HeLa cells was studied. The short-term tolerance of the implants was investigated after subcutaneous implantation in mice. The original chemical structure of etoposide was preserved after incorporation into the polymeric matrix, in which the drug was dispersed uniformly. Etoposide was present in crystalline form in the polymeric implant. In vitro release study showed prolonged and controlled release of etoposide, which showed cytotoxicity activity against HeLa cells. After implantation, good correlation between in vitro and in vivo drug release was found. The implants demonstrated good short-term tolerance in mice. These results tend to show that etoposide-loaded implants could be potentially applied as a local etoposide delivery system.

Asunto(s)

Antineoplásicos Fitogénicos/química , Portadores de Fármacos , Etopósido/química , Poliésteres/química , Animales , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Cristalización , Preparaciones de Acción Retardada , Implantes de Medicamentos , Etopósido/farmacología , Femenino , Células HeLa , Humanos , Ratones , Estructura Molecular , Poliésteres/toxicidad , Solubilidad , Tecnología Farmacéutica/métodos , Factores de Tiempo