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1.
Carbohydr Polym ; 230: 115608, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887870

RESUMO

The treatment of vulvovaginal candidiasis (VVC) is based on oral and vaginal formulations which show limited effectiveness. In this study, amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) were developed to overcome the drawbacks of the conventional formulations. AMP EUD nanoparticles/HA were synthesized by nanoprecipitation, formulated by statistical experimental design, and characterized. AMP release from EUD nanoparticles/HA and its antifungal activity in a murine model of VVC were evaluated. Nanoparticles showed 147.6 ±â€¯16.7 nm of diameter, 0.301 ±â€¯0.09 of polydispersity index, - 29.9 ±â€¯3.76 mV of zeta potential, and 87.27 % of encapsulation efficiency. They released about 81 % of AMP in 96 h; and provided the elimination of 100 % of the vaginal fungal burden in 24 h. It was suggested that the AMP EUD nanoparticles/HA penetrated into the vaginal epithelium via CD44 receptors. These AMP EUD nanoparticles/HA represent a non-conventional vaginal formulation to improve the treatment of VVC.

2.
J Dent ; 89: 103180, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415787

RESUMO

OBJECTIVE: The aim of this split-mouth, triple-blind, randomized clinical trial was to evaluate the long-term clinical efficacy of experimental potassium oxalate concentration (10%) in relieving dentin hypersensitivity (DH), after a four-session application protocol. METHODS: Potassium oxalate gels with different concentrations (5 and 10%) were randomly assigned to half of the 31 patients from the sample in a split-mouth design. The desensitizers were applied following a four-session protocol, one session every 48 h. The primary outcome was the assessment of pain level with the visual analog scale (VAS, 0-10), at baseline, immediately after each desensitizing session, and also after the seventh day and along 1-,3-, 6-, 9- and 12-months follow-ups. Statistical analyses were performed using Friedman repeated measures and Wilcoxon signed rank tests (α = 0.05). RESULTS: For both groups, the minimum of three sessions were required for the achievement of lower DH levels. Regardless of the concentration, the desensitizing effect was maintained all the way to the end of the 6-month follow-up. The 10%-potassium oxalate group was more effective for both 9 and 12-months follow-up periods (p < 0.001). No complications and adverse effects were observed. CONCLUSIONS: When a four-session protocol is applied, both concentrations of potassium oxalate (5 and 10%) proved to be effective on DH reduction for up to six months. However, the higher concentration promoted better long-term results. CLINICAL SIGNIFICANCE: The DH is an increasing condition in clinical practice, which affects the patient's life quality. This study provides primary clinical evidence, suggesting that multiple application sessions and higher concentrations of potassium oxalate may result in maintenance of the desensitizing effect for more extended periods. Trial registered under number: ClinicalTrials.gov NCT03083496.

3.
Eur J Pharm Sci ; 138: 105015, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344442

RESUMO

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.


Assuntos
Alcaloides/química , Antimaláricos/farmacologia , Mutagênicos/farmacologia , Permeabilidade/efeitos dos fármacos , Piridinas/química , Tiazóis/química , Animais , Células CACO-2 , Linhagem Celular , Linhagem Celular Tumoral , Cloroquina/farmacologia , Feminino , Hemeproteínas/química , Humanos , Malária/tratamento farmacológico , Camundongos , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos
4.
Eur J Pharm Biopharm ; 142: 20-30, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129274

RESUMO

Electrospinning technique has been explored to produce nanofibers incorporated with drugs as alternative drug delivery systems for therapeutic purposes in various organs and tissues. Before such systems could potentially be used, their biocompatibility must be evaluated. In this study, dexamethasone acetate-loaded poly(ɛ-caprolactone) nanofibers (DX PCL nanofibers) were developed for targeted delivery in the vitreous cavity in the treatment of retinal diseases. Ocular biocompatibility was tested in vitro and in vivo. DX PCL nanofibers were characterized by scanning electron microscopy (SEM) and Fourier Transform InfraRed spectroscopy (FTIR) and the in vitro drug release from nanofibers was evaluated. The in vitro biocompatibility of DX PCL nanofibers was tested on both ARPE-19 and MIO-M1 cells using the cytotoxicity (MTT) test by morphological studies based on staining of the actin fibers in ARPE-19 cells and GFAP in MIO-M1 cells. The in vivo biocompatibility of DX PCL nanofibers was investigated after intravitreous injection in the rat eye, using spectral domain Optical Coherence Tomography (OCT) imaging of the retina. SEM results indicated that nanometric fibers were interconnected in a complex network, and that they were composed of polymer. FTIR showed that polymer and drug did not chemically interact after the application of the electrospinning technique. PCL nanofibers provided controlled DX release for 10 days. DX PCL nanofibers were not cytotoxic to the ocular cells, allowing for the preservation of actin fibers and GFAP in the cytoplasm of ARPE-19 and MIO-M1 cells, respectively, which are biomarkers of these ocular cell populations. DX PCL nanofibers did not affect the retinal and choroidal structures, and they did not induce abnormalities, hemorrhages, or retinal detachment, suggesting that the nanofibers were well tolerated. In eyes receiving DX PCL nanofibers, SD-OCT images were corroborated with histological analysis of neuroretina and choroid, which are ocular tissues that are extremely sensitive to toxic agents. Finally, the preservation of cone and rod photoreceptors indicated the light sensitivity of the animals. In conclusion, DX PCL nanofibers exhibited ocular biocompatibility and safety in the rodent eye and allow the release of dexamethasone. Further studies are required to appreciate the potential of these new drug delivery systems for the treatment of retinal diseases.


Assuntos
Dexametasona/administração & dosagem , Dexametasona/química , Nanofibras/administração & dosagem , Nanofibras/química , Poliésteres/química , Retina/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Humanos , Ratos , Ratos Endogâmicos Lew , Doenças Retinianas/tratamento farmacológico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Engenharia Tecidual/métodos , Tecidos Suporte
5.
J Pharm Sci ; 107(10): 2674-2685, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29940181

RESUMO

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.


Assuntos
Anfotericina B/química , Anfotericina B/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Candidíase Vulvovaginal/tratamento farmacológico , Nanofibras/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Candida/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Testes de Sensibilidade Microbiana/métodos , Ratos , Ratos Wistar
6.
AAPS PharmSciTech ; 19(4): 1652-1661, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29516291

RESUMO

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.


Assuntos
Implantes de Medicamento/metabolismo , Etoposídeo/metabolismo , Ácido Láctico/metabolismo , Ácido Poliglicólico/metabolismo , Corpo Vítreo/metabolismo , Animais , Galinhas , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/química , Etoposídeo/administração & dosagem , Etoposídeo/química , Injeções Intravítreas , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Masculino , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Corpo Vítreo/efeitos dos fármacos
7.
Pharm Res ; 34(5): 1083-1092, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28224388

RESUMO

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.


Assuntos
Clindamicina/administração & dosagem , Clindamicina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Retina/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Células Ependimogliais , Feminino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Injeções Intravítreas/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Próteses e Implantes , Ratos , Ratos Endogâmicos Lew , Retina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/metabolismo
8.
J Pharm Sci ; 104(11): 3731-42, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26178442

RESUMO

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.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Preparações de Ação Retardada/química , Metotrexato/administração & dosagem , Poliésteres/química , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Colágeno/análise , Citocinas/análise , Sistemas de Liberação de Medicamentos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Próteses e Implantes
9.
Biomed Pharmacother ; 71: 21-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25960210

RESUMO

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.


Assuntos
Materiais Biocompatíveis/química , Inflamação/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Acetilglucosaminidase/metabolismo , Animais , Varredura Diferencial de Calorimetria , Modelos Animais de Doenças , Feminino , Hemoglobinas/metabolismo , Inflamação/patologia , Injeções Subcutâneas , Ácido Láctico/química , Camundongos , Neovascularização Patológica/patologia , Peroxidase/metabolismo , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pele/efeitos dos fármacos , Pele/patologia , Talidomida/farmacologia , Difração de Raios X
10.
Eur J Pharm Sci ; 73: 9-19, 2015 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-25797289

RESUMO

Biocompatibility is a requirement for the development of nanofibers for ophthalmic applications. In this study, nanofibers were elaborated using poly(ε-caprolactone) via electrospinning. The ocular biocompatibility of this material was investigated. MIO-M1 and ARPE-19 cell cultures were incubated with nanofibers and cellular responses were monitored by viability and morphology. The in vitro biocompatibility revealed that the nanofibers were not cytotoxic to the ocular cells. These cells exposed to the nanofibers proliferated and formed an organized monolayer. ARPE-19 and MIO-M1 cells were capable of expressing GFAP, respectively, demonstrating their functionality. Nanofibers were inserted into the vitreous cavity of the rat's eye for 10days and the in vivo biocompatibility was investigated using Optical Coherence Tomography (OCT), histology and measuring the expression of pro-inflammatory genes (IL-1ß, TNF-α, VEGF and iNOS) (real-time PCR). The OCT and the histological analyzes exhibited the preserved architecture of the tissues of the eye. The biomaterial did not elicit an inflammatory reaction and pro-inflammatory cytokines were not expressed by the retinal cells, and the other posterior tissues of the eye. Results from the biocompatibility studies indicated that the nanofibers exhibited a high degree of cellular biocompatibility and short-term intraocular tolerance, indicating that they might be applied as drug carrier for ophthalmic use.


Assuntos
Olho/efeitos dos fármacos , Nanofibras/efeitos adversos , Poliésteres/farmacologia , Animais , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Olho/citologia , Feminino , Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/metabolismo , Teste de Materiais , Neuroglia/efeitos dos fármacos , Tamanho da Partícula , Poliésteres/efeitos adversos , Ratos , Ratos Endogâmicos Lew , Retina/citologia , Retina/efeitos dos fármacos , Retina/metabolismo , Tomografia de Coerência Óptica , Corpo Vítreo/efeitos dos fármacos
11.
J Pharm Biomed Anal ; 102: 346-52, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25459934

RESUMO

Ocular toxoplasmosis may result in uveitis in the posterior segment of the eye, leading to severe visual complications. Clindamycin-loaded poly(lactide-co-glycolide) (PLGA) implants could be applied to treat the ocular toxoplasmosis. In this study, the pharmacokinetic profiles of the drug administrated by PLGA implants and by intravitreal injections in rabbits' eyes were evaluated. The implant released the drug for 6 weeks while the drug administrated by intravitreal injections remained in the vitreous cavity for 2 weeks. Compared to the injected drug, the implants containing clindamycin had higher values of area under the curve (AUC) (39.2 vs 716.7 ng week mL(-1)) and maximum vitreous concentration (Cmax) (8.7 vs 13.83 ng mL(-1)). The implants prolonged the delivery of clindamycin and increased the contact of the drug with the eyes' tissues. Moreover, the in vivo ocular biocompatibility of the clindamycin-loaded PLGA implants was evaluated regarding to the clinical examination of the eyes and the measurement of the intraocular pressure (IOP) during 6 weeks. The implantable devices caused no ocular inflammatory process and induced the increase of the IOP in the fourth week of the study. The IOP augmentation could be related to the maximum concentration of clindamycin released from the implants. In conclusion, the PLGA implants based on clindamycin may be a therapeutic alternative to treat ocular toxoplasmosis.


Assuntos
Clindamicina/análise , Clindamicina/farmacocinética , Teste de Materiais/métodos , Espectrometria de Massas em Tandem/métodos , Corpo Vítreo/química , Animais , Cromatografia Líquida/métodos , Clindamicina/química , Avaliação Pré-Clínica de Medicamentos/métodos , Implantes de Medicamento , Olho/química , Olho/efeitos dos fármacos , Injeções Intravítreas , Masculino , Coelhos , Corpo Vítreo/efeitos dos fármacos
12.
Braz Dent J ; 25(4): 327-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25250497

RESUMO

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.


Assuntos
Esmalte Dentário , Dentina , Metacrilatos , Resinas de Silorano , Resistência à Tração , Humanos , Técnicas In Vitro
13.
J Ocul Pharmacol Ther ; 30(1): 59-65, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24199740

RESUMO

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.


Assuntos
Túnica Conjuntiva/metabolismo , Córnea/metabolismo , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Administração Oftálmica , Animais , Área Sob a Curva , Linhagem Celular , Estabilidade de Medicamentos , Emulsões , Feminino , Humanos , Imunossupressores/farmacocinética , Imunossupressores/toxicidade , Tamanho da Partícula , Coelhos , Suspensões , Tacrolimo/farmacocinética , Tacrolimo/toxicidade
14.
Drug Deliv ; 20(3-4): 168-79, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23738591

RESUMO

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.


Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Metotrexato/administração & dosagem , Poliésteres/administração & dosagem , Animais , Carcinoma de Ehrlich/patologia , Implantes de Medicamento , Feminino , Células HeLa , Humanos , Metotrexato/química , Camundongos , Poliésteres/química , Resultado do Tratamento , Difração de Raios X
15.
AAPS PharmSciTech ; 14(2): 890-900, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23666789

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/química , Portadores de Fármacos , Etoposídeo/química , Poliésteres/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Cristalização , Preparações de Ação Retardada , Implantes de Medicamento , Etoposídeo/farmacologia , Feminino , Células HeLa , Humanos , Camundongos , Estrutura Molecular , Poliésteres/toxicidade , Solubilidade , Tecnologia Farmacêutica/métodos , Fatores de Tempo
16.
Gen Dent ; 61(2): 54-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23454323

RESUMO

Anterior diastemata and discolored teeth may interfere with the harmony of a person's smile. This article presents a case involving multidisciplinary intervention for esthetic treatment utilizing integrated microabrasion, dental bleaching, and restorative solutions. The relevant aspects of etiology and treatment planning are discussed.


Assuntos
Diastema/terapia , Clareamento Dental/métodos , Descoloração de Dente/terapia , Microabrasão do Esmalte , Estética Dentária , Feminino , Humanos , Adulto Jovem
17.
J Mater Sci Mater Med ; 24(5): 1309-17, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23430334

RESUMO

The subretinal transplantation of retinal pigment epithelial cells (RPE cells) grown on polymeric supports may have interest in retinal diseases affecting RPE cells. In this study, montmorillonite based polyurethane nanocomposite (PU-NC) was investigated as substrate for human RPE cell growth (ARPE-19 cells). The ARPE-19 cells were seeded on the PU-NC, and cell viability, proliferation and differentiation were investigated. The results indicated that ARPE-19 cells attached, proliferated onto the PU-NC, and expressed occludin. The in vivo ocular biocompatibility of the PU-NC was assessed by using the HET-CAM; and through its implantation under the retina. The direct application of the nanocomposite onto the CAM did not compromise the vascular tissue in the CAM surface, suggesting no ocular irritancy of the PU-NC film. The nanocomposite did not elicit any inflammatory response when implanted into the eye of rats. The PU-NC may have potential application as a substrate for RPE cell transplantation.


Assuntos
Bentonita/química , Proliferação de Células , Poliuretanos/química , Epitélio Pigmentado da Retina/fisiologia , Tecidos Suporte , Silicatos de Alumínio/síntese química , Silicatos de Alumínio/química , Silicatos de Alumínio/farmacologia , Animais , Bentonita/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Argila , Feminino , Humanos , Teste de Materiais , Nanocompostos/química , Poliuretanos/síntese química , Ratos , Ratos Endogâmicos BN , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Tecidos Suporte/química
18.
Braz Dent J ; 23(4): 403-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23207857

RESUMO

Dental ceramics present excellent ability to reproduce the natural teeth regarding esthetic and biomechanics. Recently, due to the advancement of ceramic technology, metal-free restorations were developed. However, the traditional metal-ceramic restorations still present the requirements of high strength, long survival in the oral environment and favorable aesthetics. In this context, it is essential to know the specificity of each ceramic system available in order to apply it properly to various clinical situations. This report describes an integrated rehabilitation using metal-ceramic restorations of a patient at 50 years of age, who presented edentulous spaces, and previous unsatisfactory composite and amalgam restorations, and indirect metallic restorations, leading to compromised quality of life in both functional and psychosocial aspects. The impact on quality of life was measured using a generic instrument, OHIP-14, validated for the World Health Organization, which covers both the biological and the psychosocial dimensions. This instrument was applied to the patient before and after treatment. The patient had an overall OHIP-14 score of 28 before the treatment and after treatment the score decreased to 0, showing that dental and oral health conditions are factors that do impact on the quality of life. Rehabilitation has provided functional and aesthetic restorations, harmony of the stomatognathic system and improvement of life quality.


Assuntos
Porcelana Dentária/química , Planejamento de Dentadura/psicologia , Ligas Metalo-Cerâmicas/química , Reabilitação Bucal/psicologia , Saúde Bucal , Qualidade de Vida , Antibacterianos/efeitos adversos , Atitude Frente a Saúde , Falha de Restauração Dentária , Dor Facial/reabilitação , Feminino , Seguimentos , Gengivoplastia/métodos , Humanos , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Satisfação do Paciente , Sorriso , Retalhos Cirúrgicos/cirurgia , Tetraciclina/efeitos adversos , Descoloração de Dente/induzido quimicamente , Descoloração de Dente/reabilitação , Dimensão Vertical
19.
Braz Dent J ; 23(2): 135-740, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22666771

RESUMO

In this survey, retrospective and prospective clinical studies dealing with cast-post-and core and fiber posts were reviewed regarding the rate of survival of restorations and the most prevalent failures. Electronic searches of the literature were performed in MEDLINE by crossing the key words: "Fiber post and clinical study", "Fiber post and clinical evaluation", "Cast post-and-core and clinical study", and "Root post and retrospective survival study". The cut-off dates were December 1990 through the end of December 2010. Review of literature showed that several interrelated biological, mechanical, and aesthetic factors are involved in the survival rate of restorative procedures in endodontically treated teeth, and post selection should fulfill and optimize these factors. Data based on long-term clinical studies are essential for the general practitioner when making clinical decisions. An adequate selection of teeth and post system must be made, and a minimal amount of existing tooth substance should be removed. A ferrule must be present for safe indication of the fiber posts. Fiber glass posts have demonstrated good survival in clinical studies, with similar performance to cast-post-and cores. Metallic posts have good clinical survival, but the associated failures are mostly irreversible, unlike what happens with the glass fiber posts.


Assuntos
Falha de Restauração Dentária , Técnica para Retentor Intrarradicular , Tratamento do Canal Radicular/métodos , Dente não Vital , Materiais Dentários , Falha de Restauração Dentária/classificação , Falha de Equipamento , Humanos , Falha de Tratamento
20.
J Mater Sci Mater Med ; 23(6): 1431-45, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22466817

RESUMO

The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.


Assuntos
Anti-Inflamatórios/administração & dosagem , Implantes de Medicamento , Inflamação/prevenção & controle , Neovascularização Patológica/prevenção & controle , Poliuretanos , Triancinolona Acetonida/administração & dosagem , Animais , Materiais Biocompatíveis/química , Preparações de Ação Retardada , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Implantes de Medicamento/química , Feminino , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Poliuretanos/química , Espalhamento a Baixo Ângulo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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