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Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum *** a natural transdermal penetration enhancer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2014年第2期15卷 153-164页

作者： Yi LAN Qing WU Ying-qiu MAO Qiong WANG Jing AN Yan-yan CHEN Wen-ping WANG Bo-chen ZHAO Na LIU Ye-wen ZHANG School of Chinese Materia Medica Beijing University of Chinese Medicine Center of Science Experiment Beijing University of Chinese Medicine

The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.

关键词： Zanthoxylum bungeanum Maxim. Essential oil Transdermal delivery penetration enhancer HaCaT Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR)

Investigating a Vitamin D Delivery Toothpaste Using a penetration enhancer Compound

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Advances in Bioscience and Biotechnology 2023年第1期14卷 1-17页

作者： Naree Lee Jongbin Lee Medical and Pharmaceutical Divisions STEM Science Center Englewood Cliffs NJ USA

Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.

关键词： Azone Compound Drug Delivery System Intraoral Delivery penetration enhancer Toothpaste Vitamin D

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

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Frontiers of Chemical Science and Engineering 2013年第1期7卷 29-36页

作者： Annett SCHROETER Tanja ENGELBRECHT Reinhard H. H. NEUBERT Institute of Pharmacy Martin Luther University Halle-Wittenberg D-06120 Halle/Saale Germany

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides （CER）[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid （OA） and isopropyl myristate （IPM） on the lipid nanostrueture. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. 2H NMR spectroscopy was used to study the impact of the ceramides＇ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The 2H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix. The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum comeum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases （assigned as phase A and B） appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

关键词： nano-structure of the stratum corneum cer-amide penetration enhancer model membrane neutron diffraction 2H NMR spectroscopy

Essential oil from Zanthoxylum bungeanum Maxim. and its main components used as transdermal penetration enhancers: a comparative study

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2014年第11期15卷 940-952页

作者： Yi LAN Hui LI Yan-yan CHEN Ye-wen ZHANG Na LIU Qing ZHANG Qing WU School of Chinese Materia Medica Beijing University of Chinese Medicine

Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.

关键词： Zanthoxylum bungeanum Maxim. Essential oil Limonene Fourier transform infrared (FTIR) spectroscopy penetration enhancer HaCaT

The Effects of Some penetration enhancers on the Transdermal Iontophoretic Delivery of Insulin in Vitro *

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Journal of Chinese Pharmaceutical Sciences 1996年第2期5卷 88-92页

作者：郝劲松李大为李守峰郑俊民沈阳药科大学药剂教研室沈阳东宇电子研究所

The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.

关键词： Iontophoresis penetration enhancer Insulin

Percutaneous penetration enhancement effect of essential oil of mint (Mentha haplocalyx Briq.) on Chinese herbal components with different lipophilicity

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Journal of Traditional Chinese Medical Sciences 2014年第2期1卷 109-119页

作者： Jingyan Wang Yi Lan Hui Li Yewen Zhang Qing Zhang Yanfeng Cao Qing Wu Department of Pharmaceutics School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100102China Department of Pharmacy and Forensic Science King’s College LondonLondon WC2R2LSUK

Objective:To investigate the percutaneous penetration effect of essential oil of mint from Mentha haplocalyx *** the complex active components in Chinese herbal external preparations,and assess its toxicity on the skin ***:The cytotoxicity of mint oil on HaCaT keratinocytes and CCC-ESF-1 fibroblasts was measured using an MTT *** model drugs with a wide range of lipophilicity,namely osthole,tetramethylpyrazine,ferulic acid,puerarin,and geniposide,were tested using in vitro permeation studies to investigate the percutaneous penetration enhancement effect of mint *** structure alterations of skin stratum corneum(SC)were measured using Fourier transform infrared spectroscopy(FTIR).Saturation solubilities and SC/vehicle partition coefficients of the five model drugs with and without mint oil were also determined to understand the potential mechanisms of the essential ***:Half maximal inhibitory concentration(IC50)values of mint oil were significantly higher in HaCaT and CCC-ESF-1 cell lines than values in the well-established and standard penetration enhancer ***:Mint oil at proper concentration could effectively facilitate percutaneous penetration of both lipophilic and hydrophilic drugs,and exhibit higher efficiency for moderate hydrophilic *** of penetration enhancement by mint oil could be explained with saturation solubility,SC/vehicle partition coefficient and the secondary structure change of SC.

关键词： Mint Essential oil penetration enhancer Transdermal delivery Fourier transform infrared spectroscopy

Efficacy and mechanism of methyl salicylate in the enhancement of skin delivery of herbal medicines

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Journal of Traditional Chinese Medical Sciences 2021年第4期8卷 336-342页

作者： Jingyan Wang Xinyu Zhao Jiajia Chen Xin Li Doudou Hao Tingting Li Kai Mei Yi Lan Qing Wu Department of TCM Pharmaceutics School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing102488China Beijing Children's Hospital Capital Medical UniversityBeijing100045China Pharmaceutical Technology and Development Beijing Fengke Ruitai Pharmaceutical Technology Co.Ltd.Beijing100070China

Objective: To elucidate the molecular mechanism(s) by which methyl salicylate enhances the skin delivery of herbal ingredients with diverse ***: The toxicity of methyl salicylate on skin cell lines was evaluated using the MTT assay. The Franz diffusion cell method was used to measure the permeability enhancing activities of methyl salicylate for five herbal ingredients with a range of lipophilicities. The interaction between methyl salicylate and the stratum corneum(SC) was observed by using an infrared spectroscopy technique. Moreover, the solubilities and SC-vehicle partition coefficient were determined to monitor the impact of methyl salicylate on the drug thermodynamic activities and partition into the SC layer, ***: Compared with azone(1-dodecylazacycloheptan-2-one), methyl salicylate showed lower toxicity to skin cells in terms of the IC50 values. The in vitro skin permeation studies showed that methyl salicylate could greatly improve the cumulative amounts or steady state flux of the selected model drugs with the exception of osthole, which indicated that methyl salicylate was prone to promote the skin delivery of hydrophilic drugs. The Fourier transform infrared spectroscopy studies revealed that methyl salicylate mainly interacted with SC lipids, leading to the disruption of the orderly arrangement of the *** addition, methyl salicylate had no obvious effect on the drug thermodynamic activity and partition into the ***: Methyl salicylate could effectively promote the skin delivery of relatively hydrophilic ingredients in externally used traditional Chinese medicines(TCM) without obvious cytotoxicity.

关键词： Methyl salicylate Transdermal delivery penetration enhancer Stratum corneum Fourier transform infrared spectroscopy

Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

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Journal of Traditional Chinese Medical Sciences 2016年第3期3卷 157-167页

作者： Yi Lan Jingyan Wang Shuwang He Shuying Li Peng Tan Hongmei Lin Qing Wu Department of Pharmaceutics School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100102PR China Shandong Dyne Marine Biopharmaceutical Co.Ltd WeihaiShandong 264300PR China

Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(*** oil)on active components in externally-applied traditional Chinese ***:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal *** electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with *** *** molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of ***:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of *** treatment with *** oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration *** was no significant difference between the control and the *** oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration *** oxygen-containing constituents in *** oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide ***:*** oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic *** mechanisms of transdermal permeation enhancement by the

关键词： Zanthoxylum bungeanum Maxim. Essential oil penetration enhancer Transdermal delivery Molecular dynamic simulation

花椒挥发油作为天然经皮促渗剂的细胞毒性及其促渗机理研究(英文)

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花椒挥发油作为天然经皮促渗剂的细胞毒性及其促渗机理研究(英文)