Penetration of chlorhexidine into human skin

This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 µm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 ± 0.047 and 0.077 ± 0.015 µg/mg tissue within the top 100 µm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 µg/mg tissue below 300 µm). After 24 h of exposure, there was more chlorhexidine within the upper 100-µm sections (7.88 ± 1.37 µg/mg tissue); however, the levels remained low (less than 1 µg/mg tissue) at depths below 300 µm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.

Studies of skin antisepsis and enhanced penetration of chlorhexidine

Current evidence-based guidelines recommend that 2% (w/v) chlorhexidine digluconate (CHG), preferentially in 70% (v/v) isopropyl alcohol (IIPA), is used for skin antisepsis prior to incision of the skin. In this current study, the antimicrobial efficacy of CHG, six essential oils [tea tree oil (TTO), thymol, eucalyptus oil (EO), juniper oil, lavender oil and citronella] and novel benzylidenecarboxamidrazone and thiosemicarbazone compounds were determined against a panel of microorganisms commonly associated with skin infection (Staphylococcus epidermidis, S. aureus, meticillin-resistant S. aureus, Propionibacterium acnes, Acinetobacter spp., Pseudomonas aeruginosa and Candida albicans) The results demonstrated synergistic activity of CHG in combination with EO against biofilm cultures of S. epidermidis, with significantly reduced concentrations of CHG and EO required to inhibit biofilm growth compared to CHG or EO alone. Skin permeation of CHG was subsequently investigated using an in vitro human skin model (Franz cell) and the penetration profile was determined by serial sectioning of the full thickness human skin. Two percent (w/v) CHG in aqueous solution and in 70% (v/v) IPA demonstrated poor skin permeation; however, the skin permeation was significantly enhanced in combination with 5% - 50% (v/v) EO. Detectable levels of CHG did not permeate through full thickness skin in 24 h. Skin permeation of 2% (w/v) CHG in 70% (v/v) IPA in the presence of 10% (v/v) EO was subsequently studied. The results demonstrated a significantly enhanced skin penetration of CHG after a 2 min application, with CHG detected at significant levels to a depth of 600 m with CHG in combination with EO and IPA compared to 100 m with IPA alone. Combination antisepsis comprising CHG and EO may be beneficial for skin antisepsis prior to invasive procedures to reduce the number of microorganisms on and within the skin due to enhanced skin penetration of CHG and improved efficacy against S. epidermidis in a biofilm mode of growth.

Influence of Urea, Isopropanol, and Propylene Glycol on Rutin In Vitro Release from Cosmetic Semisolid Systems Estimated by Factorial Design

Rutin, one of the major flavonoids found in an assortment of plants, was reported to act as a sun protection factor booster with high anti-UVA defense, antioxidant, antiaging, and anticellulite, by improvement of the cutaneous microcirculation. This research work aimed at evaluating the rutin in vitro release from semisolid systems, in vertical diffusion cells, containing urea, isopropanol and propylene glycol, associated or not, according to the factorial design with two levels with center point. Urea (alone and in association with isopropanol and propylene glycol) and isopropanol (alone and in association with propylene glycol) influenced significant and negatively rutin liberation in diverse parameters: flux (g/cm2.h); apparent permeability coefficient (cm/h); rutin amount released (g/cm2); and liberation enhancement factor. In accordance with the results, the presence of propylene glycol 5.0% (wt/wt) presented statistically favorable to promote rutin release from this semisolid system with flux = 105.12 8.59 g/cm2.h; apparent permeability coefficient = 7.01 0.572 cm/h; rutin amount released = 648.80 53.01 g/cm2; and liberation enhancement factor = 1.21 0.07.

Optimization of Pothomorphe umbellata (L.) Miquel topical formulations using experimental design

Pothomorphe umbellata is a native plant widely employed in the Brazilian popular medicine. This plant has been shown to exert a potent antioxidant activity on the skin and to delay the onset and reduce the incidence of UVB-induced skin damage and photoaging. The aim of this work was to optimize the appearance, the centrifuge stability and the permeation of emulsions containing R umbellata (0. 1% 4-nerolidylchatecol). Experimental design was used to study ternary mixtures models with constraints and graphical representation by phase diagrams. The constraints reduce the possible experimental domain, and for this reason, this methodology offers the maximum information while requiring the minimum investment. The results showed that the appearance follows a linear model, and that the aqueous phase was the principal factor affecting the appearance; the centrifuge stability parameter followed a mathernatic quadratic model and the interactions between factors produced the most stable emulsions; skin permeation was improved by the oil phase, following a linear model generated by data analysis. We propose as optimized P. umbellata formulation: 68.4% aqueous phase, 26.6% oil phase and 5.0% of self-emulsifying phase. This formulation displayed an acceptable compromise between factors and responses investigated. (c) 2007 Elsevier B.V. All rights reserved.

Development of microemulsions to topically deliver 5-aminolevulinic acid in photodynamic therapy

The aim of this study was to obtain and to characterize microemulsions containing 5-aminolevulinic acid (5-ALA) and to investigate the influence of these systems in drug skin permeation for further topical photodynamic therapy (PDT). 5-ALA was incorporated in water-in-oil (W/O), bicontinuous (Bc), and oil-in-water (O/W) microemulsions obtained by the titration of ethyl oleate and PEG-8 caprylic/capric glycerides:polyglyceryl-6 dioleate (3:1) mixtures with water. Selected systems were characterized by conductivity, viscosity, size of the droplets, and drug release. The stability of the drug in the microemulsions was also assessed. Moreover, the in vitro and in vivo skin permeation of 5-ALA was investigated using diffusion cells and confocal scanning laser microscopy (CSLM), respectively. Despite the fact that the O/W microemulsion decreased the 5-ALA diffusion coefficient and retarded the drug release, it also significantly increased the in vitro drug skin permeation when compared to other 5-ALA carriers. It was observed by CSLM that the red fluorescence of the skin increased homogeneously in the deeper skin layers when the 5-ALA microemulsion was applied in vivo, probably due to the formation of the photoactive protoporphyrin IX. The microemulsion developed carried 5-ALA to the deeper skin layers, increasing the red fluorescence of the skin and indicating the potentiality of the system for topical 5-ALA-PDT. (C) 2010 Elsevier B.V. All rights reserved.

Effect of vehicle pretreatment on the flux, retention, and diffusion of topically applied penetrants in vitro

Purpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log K-oct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm(3))(1/2). Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log K-oct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

Evaluation of respiratory and dermal occupational exposures to monoethanolamine during cleaning

Professional cleaning is a basic service occupation with a wide variety of tasks carried out in all kind of different sectors and workplaces by a large workforce. One important risk for cleaning workers is the exposure to chemical substances that are present in cleaning products.Monoethanolamine was found to be often present in cleaning products such as general purpose cleaners, bathroom cleaners, floor cleaners and kitchen cleaners. Monoethanolamine can injure the skin, and exposure to monoethanolamine was associated to asthma even when the air concentrations were low. It is a strong irritant and known to be involved in sensitizing mechanisms. It is very likely that the use of cleaning products containing monoethanolamine gives rise to respiratory and dermal exposures. Therefore there is a need to further investigate the exposures to monoethanolamine for both, respiratory and dermal exposure.The determination of monoethanolamine has traditionally been difficult and analytical methods available are little adapted for occupational exposure assessments. For monoethanolamine air concentrations, a sampling and analytical method was already available and could be used. However, a method to analyses samples for skin exposure assessments as well as samples of skin permeation experiments was missing. Therefore one main objective of this master thesis was to search an already developed and described analytical method for the measurement of monoethanolamine in water solutions, and to set it up in the laboratory. Monoethanolamine was analyzed after a derivatisation reaction with o-pthtaldialdehyde. The derivated fluorescing monoethanolamine was then separated with high performance liquid chromatography and detection took place with a fluorescent detector. The method was found to be suitable for qualitative and quantitative analysis of monoethanolamine. An exposure assessment was conducted in the cleaning sector to measure the respiratory and dermal exposures to monoethanolamine during floor cleaning. Stationary air samples (n=36) were collected in 8 companies and samples for dermal exposures (n=12) were collected in two companies. Air concentrations (Mean = 0.18 mg/m3, Standard Deviation = 0.23 mg/m3, geometric Mean = 0.09 mg/m3, Geometric Standard Deviation = 3.50) detected were mostly below 1/10 of the Swiss 8h time weighted average occupational exposure limit. Factors that influenced the measured monoethanolamine air concentrations were room size, ventilation system and the concentration of monoethanolamine in the cleaning product and amount of monoethanolamine used. Measured skin exposures ranged from 0.6 to 128.4 mg/sample. Some cleaning workers that participated in the skin exposure assessment did not use gloves and had direct contact with the solutions containing the cleaning product and monoethanolamine. During the entire sampling campaign, cleaning workers mostly did not use gloves. Cleaning workers are at risk to be regularly exposed to low air concentrations of monoethanolamine. This exposure may be problematic if a worker suffers from allergic reactions (e.g. Asthma). In that case a substitution of the cleaning product may be a good prevention measure as several different cleaning products are available for similar cleaning tasks. Currently there are no occupational exposure limits to compare the skin exposures that were found. To prevent skin exposures, adaptations of the cleaning techniques and the use of gloves should be considered. The simultaneous skin and airborne exposures might accelerate adverse health effects. Overall the risks caused by exposures to monoethanolamine are considered as low to moderate when the cleaning products are used correctly. Whenever possible, skin exposures should be avoided. Further research should consider especially the dermal exposure routes, as very high exposures might occur by skin contact with cleaning products. Dermatitis but also sensitization might be caused by skin exposures. In addition, new biomedical insights are needed to better understand the risks of the dermal exposure. Therefore skin permeability experiments should be considered.

A web-based tool to aid the identification of chemicals potentially posing a health risk through percutaneous exposure

Occupational hygiene practitioners typically assess the risk posed by occupational exposure by comparing exposure measurements to regulatory occupational exposure limits (OELs). In most jurisdictions, OELs are only available for exposure by the inhalation pathway. Skin notations are used to indicate substances for which dermal exposure may lead to health effects. However, these notations are either present or absent and provide no indication of acceptable levels of exposure. Furthermore, the methodology and framework for assigning skin notation differ widely across jurisdictions resulting in inconsistencies in the substances that carry notations. The UPERCUT tool was developed in response to these limitations. It helps occupational health stakeholders to assess the hazard associated with dermal exposure to chemicals. UPERCUT integrates dermal quantitative structure-activity relationships (QSARs) and toxicological data to provide users with a skin hazard index called the dermal hazard ratio (DHR) for the substance and scenario of interest. The DHR is the ratio between the estimated 'received' dose and the 'acceptable' dose. The 'received' dose is estimated using physico-chemical data and information on the exposure scenario provided by the user (body parts exposure and exposure duration), and the 'acceptable' dose is estimated using inhalation OELs and toxicological data. The uncertainty surrounding the DHR is estimated with Monte Carlo simulation. Additional information on the selected substances includes intrinsic skin permeation potential of the substance and the existence of skin notations. UPERCUT is the only available tool that estimates the absorbed dose and compares this to an acceptable dose. In the absence of dermal OELs it provides a systematic and simple approach for screening dermal exposure scenarios for 1686 substances.

Desenvolvimento e atividade do fitocosmético contendo licopeno para o combate à aceleração do envelhecimento cutâneo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência da associação de filtros solares sobre a estabilidade, liberação, permeação e retenção cutânea do p-metoxicinamato de octila em formulações fotoprotetoras

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da segurança e estudo da permeação e retenção cutânea de géis de ácido hialurônico

Pós-graduação em Ciências Farmacêuticas - FCFAR

Avaliação da atividade antiproliferativa in vitro, liberação, permeação e retenção cutânea in vitro e estabilidade de emulsões contendo (-)- Terpinen-4-OL

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Membranas de celulose bacteriana contendo nanopartículas de 'YVO IND. 4': 'YB POT. 3+': 'ER POT. 3+'/'HO POT. 3+' para aplicações envolvendo conversão ascendente de energia

Pós-graduação em Química - IQ

Estudo da eficácia e citotoxicidade de filme e sistema emulsionado contendo ácido cafeico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento e caracterização de nanopartículas lipídicas sólidas para administração cutânea de trans-resveratrol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)