The combination of iontophoresis with solid lipid nanoparticles (SLNs) for targeting drug delivery to the epidermis has not been explored. The goal of this paper was to study the influence of iontophoresis on the penetration of doxorubicin (DOX) delivered in SLNs (DOX-SLNs). We measured the contribution of electroosmotic flow to the transport of DOX, and the accumulation of DOX in the stratum corneum (SC) and in the viable epidermis was determined. In addition, we evaluated the cytotoxicity of DOX-SLNs against skin cancer cells. Iontophoresis of unloaded SLNs decreased the electroosmotic flow by a factor of 5 and increased the skin resistance. Nevertheless, iontophoresis of DOX-SLNs increased DOX delivery to the viable epidermis, with 56% of all DOX penetrating this skin layer. Only 26% of the drug was retained in the SC. In contrast, passive delivery retained 43% of DOX in the SC and 26% in the viable epidermis. DOX-SLNs increased DOX cytotoxicity against melanoma cells by 50%. These results suggest the use of DOX-SLN iontophoresis in the topical treatment of skin cancer.
Nitric oxide (NO) is a gaseous molecule that has specific functions dictated by its localization and its kinetics of release. As NO-donors have a range of potential uses in the skin, much attention has been paid to the development of topical NO delivery systems. The aim of this work was to study the release rate and the skin penetration of the NO-donor cis-[Ru(NO(2))(bpy)(2)(4-pic)](+) from different gel formulations and their potential as topical NO delivery systems under light stimuli. Among the formulations developed, the anionic gel retarded the nitro-ruthenium complex diffusion and also obstructed NO release after light irradiation. On the other hand, NO release before light irradiation was observed when the complex was dispersed in the cationic chitosan gel, possibly due to oxi-redox reactions between the amino groups of the polymer and the drug molecule. Finally, the non-ionic gel released the NO after light irradiation to the same extent as a drug aqueous solution at the same pH. The drug dispersed in this gel also penetrated into the stratum corneum skin layer, and the nitro-ruthenium complex present in the skin was able to release the NO after light stimuli, suggesting the potential use of this formulation as a topical NO delivery system.
Ruthenium (Ru) complexes have been studied as promising anticancer agents. Ru nitrosyl complex (Ru-NO) is one which acts as a pro-drug for the release of nitric oxide (NO). The Ru-aqueous complex formed by the exchange of NO for a water molecule after NO release could also possess therapeutic effects. This study evaluates the influence of iontophoresis on enhancing the skin penetration of Ru-NO and Ru-aqueous and assesses its applicability as a tool in treating diverse skin diseases. Passive and iontophoretic (0.5 mA·cm−2) skin permeation of the complexes were performed for 4 h. The amount of Ru and NO in the stratum corneum (SC), viable epidermis (VE), and receptor solution was quantified while the influence of iontophoresis and irradiation on NO release from Ru-NO complex was also evaluated. Iontophoresis increased the amount of Ru-NO and Ru-aqueous recovered from the receptor solution by 15 and 400 times, respectively, as compared to passive permeation. Iontophoresis produced a higher accumulation of Ru-aqueous in the skin layers as compared to Ru-NO. At least 50% of Ru-NO penetrated the SC was stable after 4 h. The presence of Ru-NO in this skin layer suggests that further controlled release of NO can be achieved by photo-stimulation after iontophoresis.
The aim of this paper is to determine the profile of acute alcohol poisoning and to estimate the risk of potentially adverse drug interactions (ADIs) in patients intoxicated by alcohol when attended in emergency care at hospital. A descriptive serial cross-sectional study was performed with 4,271 individuals intoxicated by alcohol, from January 2009 to July 2011. Possible correlations were measured by Pearson's chi-square test. The data show high consumption in the population, especially in males between 25 and 59 years. The main circumstances for poisoning were alcohol misuse (96.3%). After treatment complete recovery from the signs or symptoms of the poisoning was observed in 96.88% cases; and death in 0.70%. The demonstration of potential risk for ADIs in medical care included 300 medical records which contained a history of acute alcohol poisoning. Possible drug-drug interactions (44.2%) and drug-alcohol interactions (55.8%) were demonstrated in 60.60% of analyzed medical records. Among these cases, 3%, 92.4% and 4.6% were classified as mild, moderate and severe, respectively. The measurement of ADIs aims to prevent clinical complications in medical care for alcohol misuse disorders.Uniterms: Alcoholic intoxication. Emergency Medical Services. Risk Management. Medicines/adverse interactions/risk control. Medicines/alcohol interactions/risk control. O objetivo deste trabalho foi definir o perfil de intoxicação alcoólica aguda e estimar o risco de interações medicamentosas adversas (IMAs) potenciais em pacientes com intoxicação alcoólica atendidos na emergência hospitalar. Um estudo descritivo, serial, de corte transversal foi realizado com 4.271 indivíduos com intoxicação alcoólica, de janeiro 2009 a julho 2011. Correlações foram medidas pelo teste qui-quadrado. Os dados mostram alto consumo na população estudada, especialmente em homens de 25 a 59 anos. A principal circunstância de intoxicação foi o abuso (96,3%). Após tratamento, cura foi observada em 96,88% dos casos e morte em 0,7%. O risco de IMAs potenciais no atendimento médico incluiu 300 prontuários médicos com histórico de intoxicação alcoólica aguda. Possíveis interações medicamentosas (44,2%) e interações fármaco-álcool (55,8%) foram observadas em 60,6% dos prontuários analisados. Entre elas, 3%, 92,4% e 4,6% foram classificadas como leve, moderada e grave, respectivamente. A medição das IMAs visa a prevenir complicações clínicas no atendimento dos agravos devido ao abuso de álcool.Unitermos: Intoxicação alcoólica. Serviços Médicos de Emergência. Medicamentos/interações adversas/ controle de risco. Medicamentos/interação com álcool/controle de risco.
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