Safety and efficacy of erythroxylum cuneatum / Wesam Radhi Kadhum

Erythroxylum cuneatum is a member of a tropical plant family which is considered to be a good source of phenolic compounds. The aims of this study were to determine the in vitro cytotoxicity, cytoprotective activity, genotoxicity and antioxidant enzymes specific activities of the standardized aqueous extract of E. cuneatum. In vitro toxicity of E. cuneatum extract in four cultured cell lines was determined. The IC50 values in the various cell lines were all higher than 100 µg/ml, indicating low cytotoxic effects. The cytoprotective activity was determined by treating four cultured cell lines (leukemia cells, colon cancer cells, liver cancer cells and normal liver cells) with hydrogen peroxide H2O2 (28-158 µM) and determining the effects of E. cuneatum (5-50 µg/ml) in the H2O2 treated cells. The results showed that H2O2 was cytotoxic to cells and the addition of E. cuneatum reduced its cytotoxicity. The cytoprotective activity was also determined by treating cultured cell lines (liver cancer cells and normal liver cells) with menadione (2methyl- l A-naphthoquinone) (12-30 µM) and determining the effects of the extract (5-50 µg/ml) in the menadione-treated cells. Results showed that the extract, was not able to rescue cells from the cytotoxicity effects of menadione. Genotoxicity of the extract in HepG2 and WRL68 cell lines were assessed by single cell gel electrophoresis (comet assay), whereby cells were treated with hydrogen peroxide (50 µM) as genotoxic control and different concentrations of E. cuneatum (0.005-1 mg/ml). A low level of DNA damage was seen at the highest concentration of 1 mg/ml while no DNA damage was seen at the other concentrations. E. cuneatum 50 µg/ml when incubated with normal and cancer liver cells significantly increased in catalase specific activity but did not affect cellular GPx and SOD activities. E. cuneatum standardized aqueous extract was found to be non cytotoxic and non genotoxic, showed protection to HepG2 and HCT116 cells from H2O2- induced toxicity but did alter menadione induced cell death. E. cuneatum (50 µg/ml) elevated catalase specific activity in HepG2 and WRL68 cells. More studies are needed if E. cuneatum is to be developed as a cytoprotectant

Sensor Activity Scheduling Protocol for Lifetime prolongation in Wireless Sensor Networks

In Wireless Sensor Network (WSN), the dense sensor nodes deployment in the sensing field can be exploited in conserving the energy of the whole network, where the data of these nodes can be highly correlated. Therefore, it is necessary to turn off the unnecessary nodes that sense similar sensor readings so as to reduce the redundant sensed readings and decrease the communication overhead thus extend the WSN lifetime. This article suggests a Sensor Activity Scheduling (SAS) protocol for lifetime improvement of WSNs. SAS works in a periodic way. It exploits the spatial correlation among sensed sensor data in order to produce the best sensor activities schedule in WSNs. SAS composed of three phases: data collection, decision-based optimization, and sensing. SAS measures the similarity degree among the sensed data that collected in the first phase. It makes a decision of which sensors stay active during the sensing phase in each period and put the other nodes into low power sleep whilst keeping a good accuracy level to the received data at the sink to conserve the power and enhance the lifetime of the WSN. Several experiments based on real sensed data and by using OMNeT++ simulator demonstrate that SAS can save energy and extend the WSN lifetime efficiently compared with the other methods

Potential of imaging analysis in establishing skin concentration-distance profiles for topically applied FITC-dextran 4 kDa

Quantitatively determining the skin concentration-distance profiles of topically applied drugs is important for evaluating their safety and efficacy. The aim of the present study was to quantitatively visualize the distribution of hydrophilic drugs through the skin using confocal laser scanning microscopy (CLSM) in order to obtain skin concentration-distance profiles. FITC-dextran with a molecular weight of approximately 4 kDa (FD-4) was selected as the model fluorescent drug in the present study, and excised pig ear skin was used. The skin concentration of FD-4 at each depth of a skin section was assessed by imaging analysis of the intensity of fluorescence. The FD-4 skin concentration-distance profile obtained was analyzed using Fick’s second law of diffusion, and was markedly similar to that using skin permeation parameters in the skin permeation study. These results suggest that the present CLSM method may be a promising tool for quantitatively visualizing the concentration-distance profiles of drugs through the skin

Development and optimization of orally and topically applied liquid crystal-drug formulations

学位授与機関：城西大学 学位記番号：博乙第79号，学位の種別：博士（薬科学）， 学位授与年月日： 平成29年(2017年)9月20日 (94p.)博士（薬科学）城西大

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane) and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane) and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.Open Access Journa

In Vitro and In Silico Approaches to Evaluate Usefulness and Safety of Chemical Compounds Applied or Exposed on Skin

Recently, animal experiments become very difficult to be done in the research and development of cosmetics and cosmeceuticals due to animal welfare and 3Rs (replacement, reduction, refinement) concept. However, usefulness and safety of these preparations must be strictly guaranteed before human use. We thus proposed three sets of extrapolation methods to estimate in vivo profiles from in vitro and in silico approaches, to evaluate permeation profiles through real human skin from those through animal skin and cultured human skin model, and to estimate responses such as usefulness and safety of cosmetics and cosmeceuticals from their skin permeation and concentration profiles. Although we need more data and discussion, the present extrapolation methods must be very useful for estimation of cosmetics and cosmeceuticals without using animal experiments.本総説は、日本薬学会第133年会シンポジウムS29-103で発表した内容を中心に記述したものである

Usefulness of liquid–crystal oral formulations to enhance the bioavailability and skin tissue targeting of p-amino benzoic acid as a model compound

Topical formulations are not always suitable to deliver active ingredients to large areas of skin. Thus, in this study, we aimed to develop an oral formulation for skin tissue targeting with a high bioavailability using liquid crystal (LC) dispersions comprising cubosomes of a mal-absorptive model compound, p-amino benzoic acid (PABA), which is an active element in cosmeceuticals, dietary supplements and skin disorder medicines. The bioavailability and skin concentration of PABA were investigated after oral administration in rats. The effect of the remaining amount of the LC formulation in the stomach on the pharmacokinetic profiles of orally administered PABA was evaluated. The skin permeation and concentration of PABA were also investigated using an in vitro permeation experiment. As a result, the bioavailability of PABA was significantly improved by administration of PABA-LC formulations compared with PABA solution alone, although the effect was greatly influenced by the type of LC-forming lipids. The in vitro skin permeation study showed that the PABA concentration in the skin when applied from the dermis side was higher than when applied from the epidermis side. These findings suggested that oral administration advantageously supports skin targeting, and oral LC formulations could be a promising material in cosmeceutical, dietary and clinical fields