RESUMO
The widespread use of indwelling medical devices has enormously increased the interest in materials incorporating antibiotics and antimicrobial agents as a means to prevent dangerous device-related infections. Recently, chlorhexidine-loaded polyurethane has been proposed as a material suitable for the production of devices which are able to resist microbial contamination. The aim of the present study was to characterize the in vitro release of chlorhexidine from new polymeric orthodontic chains realized with polyurethane loaded with two different chlorhexidine salts: chlorhexidine diacetate or chlorhexidine digluconate. The orthodontic chains constituted of three layers: a middle polyurethane layer loaded with chlorhexidine salt inserted between two layers of unloaded polymer. In vitro release of chlorhexidine diacetate and digluconate from orthodontic chains loaded with 10% or 20% (w/w) chlorhexidine salt was sustained for 42 days and followed Fickian diffusion. The drug diffusion through the polyurethane was found to be dependent not only on chlorhexidine loading, but also on the type of chlorhexidine salt. The antibacterial activity of 0.2% (w/w) chlorhexidine diacetate-loaded orthodontic chain was successfully tested towards clinically isolated biofilm forming ica-positive Staphylococcus epidermidis via agar diffusion test. In conclusion, the chlorhexidine salt-loaded chains could provide an innovative approach in the prevention of oral infections related to the use of orthodontic devices.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Clorexidina/análogos & derivados , Clorexidina/química , Clorexidina/farmacologia , Poliuretanos/química , Antibacterianos/administração & dosagem , Biofilmes/efeitos dos fármacos , Clorexidina/administração & dosagem , Humanos , Cinética , Polímeros/química , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus epidermidis/fisiologiaRESUMO
CONTEXT: Temozolomide (TMZ) is approved for the treatment of high-grade gliomas such as glioblastoma (GBM) multiforme and refractory anaplastic astrocytoma, but it is also used in indications not mentioned in the summary of product characteristics (SPC). The main objective of this study was to evaluate the conformity of TMZ prescriptions to the French SPC and prescription guidebook. METHODS: We conducted a prospective observational study of all consecutive patients treated with TMZ in 21 French hospitals between September 2006 and February 2007, accounting for 39% of total TMZ consumption in France. The conformity of TMZ prescriptions was evaluated in terms of the indication, dosage, treatment duration, and combination with other treatments, with respect to the SPC and prescription guidebook. RESULTS: We enrolled 831 patients (median age, 56 years) who received a total of 5982 TMZ treatment cycles. TMZ was mainly prescribed to patients with newly diagnosed GBM (384 patients), GBM in progression/relapse (28 patients), or anaplastic astrocytoma in progression/relapse (19 patients). Prescriptions conformed to the SPC in 51.9% of cases and to the prescription guidebook in 91.5% of cases. Global conformity with the SPC, in terms of the dosage, treatment duration, and combination with other treatments, was 62% for newly diagnosed GBM treated with radiotherapy plus TMZ, 72% for TMZ maintenance monotherapy, and 66% for GBM and anaplastic astrocytoma in progression/relapse. CONCLUSION/DISCUSSION: In France, routine TMZ prescriptions conform to the SPC and practice guidebook. This is one of the largest studies of drug use in neuro-oncology in terms of the number of patients and cycles analyzed.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Dacarbazina/análogos & derivados , Glioma/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Uso Off-Label/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Esquema de Medicação , Uso de Medicamentos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Prospectivos , TemozolomidaRESUMO
Often presented as metabolism byproducts, reactive oxygen species are linked to detrimental effects such as chronic wound, mutagenesis, cancer and skin ageing. However, recent in vitro and in vivo observations suggest that ROS, and mainly hydrogen peroxide, interfere with cell signaling acting like second messenger and inducing adaptive responses. This is particularly observed in skin wound healing where cells are exposed to H2O2 following injury. In this study, we developed and characterized an innovative formulation producing H2O2 at low concentrations, in order to mimic physiological inflammation phase. Then, this pro-oxidative formulation (CAM-GOx) was assayed in vitro on keratinocytes cell culture, compared to the blank formulation (CAM) and the anti-oxidative formulation (CAM-CAT) to assess whether oxidative stress was implied or not in cellular responses.
Assuntos
Estresse Oxidativo/fisiologia , Cicatrização/fisiologia , Alginatos , Ensaios de Migração Celular , Células Cultivadas , Quitosana , Humanos , Peróxido de Hidrogênio/metabolismo , Queratinócitos/citologia , Microesferas , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment.
Assuntos
Composição de Medicamentos/métodos , Minoxidil/farmacocinética , Nanopartículas/química , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Suspensões/farmacocinética , Administração Cutânea , Animais , Cultura em Câmaras de Difusão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Lipídeos/administração & dosagem , Lipídeos/efeitos adversos , Lipídeos/química , Lipídeos/farmacocinética , Minoxidil/administração & dosagem , Minoxidil/efeitos adversos , Minoxidil/química , Nanopartículas/administração & dosagem , Nanopartículas/efeitos adversos , Tamanho da Partícula , Pele/patologia , Testes de Irritação da Pele/métodos , Soluções/administração & dosagem , Soluções/efeitos adversos , Soluções/farmacocinética , Suspensões/administração & dosagem , Suspensões/efeitos adversos , Suspensões/síntese química , SuínosRESUMO
In our hospital, in accordance with recommendations for personnel protection, hazardous drugs are prepared in a class II biological safety cabinet (BSC) located in a specific area of the pharmacy. The aim of this study was to validate the efficiency of this unit in personnel protection by measuring levels of platinum in the working environment (platinum being the most common antineoplastic agent used in this hospital). Two series of surface sampling were conducted, preparation guidelines were changed for parts after first results have been completed. Performance of the sampling method is about 35%. Platinum was measured by atomic absorption spectrophotometry technique. The analytical detection limit was 10 mug/L of platinum and was sufficient to detect less than one micro-drop of cisplatinum solution (1 mg/mL). Platinum was found inside the BSC at the end of the working day: 2 to 998 pg/cm2 or 2 to 20 ppm of the total cisplatinum handled. All samples outside the BSC showed little (less than the detection limit) or no contamination. Gloves were often contaminated, either by contaminated commercial drug vials or through handling errors. Working guidelines changes did not lead to the absence contamination on surfaces. Gloves should therefore be changed frequently (every 15 min), personnel training should be regularly re-evaluated, BSC and rooms should be thoroughly cleaned every day. In this way, a centralized unit provides total protection from exposure to hazardous drugs.