Investigating a Vitamin D Delivery Toothpaste Using a Penetration Enhancer Compound

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.

The Effects of Some Penetration Enhancers on the Transdermal Iontophoretic Delivery of Insulin in Vitro *

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.

IMPROVE OPTICAL CLEARING OF SKIN IN VITRO WITH PROPYLENE GLYCOL AS A PENETRATION ENHANCER

In order to enhance the optical clearing effect of topically applied optical clearing agents(OCAs),we evaluated the effect of propylene glycol(PG)as a chemical penetration enhancer(PE)on optical clearing of skin in vitro by observation and measurement of optical-transmittance and diffuse-reflectance spectra.Three OCAs,i.e.,glycerol,D-sorbitol and PEG400,and two other penetration enhancers,Azone and Thiazone,were used in this study.The results indicated that the decrease of reduced scattering coefficient caused by OCA/PG was larger than that by pure OCA,and the change by OCA/water was the least after the same treatment time.There were significant differences for the reduced scattering coefficient at 630 nm after 120 min application of agents between OCA and OCA/PG.The efficacy of optical clearing caused by OCA/PG depended on the OCA itself.When PEG400 was mixed with three different PEs,we found the optical clearing were different.The penetration enhancing ability of PG was much better compared to Azone,and suboptimal to Thiazone.Also,this study provides evidence for the use of PG as a PE in order to improve skin optical clearing.

Influence of chemical penetration enhancers on skin permeability of ellagic acid-loaded niosomes

This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4
C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.

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

Objective:To investigate the percutaneous penetration effect of essential oil of mint from Mentha haplocalyx Briq.on the complex active components in Chinese herbal external preparations,and assess its toxicity on the skin cells.Methods:The cytotoxicity of mint oil on HaCaT keratinocytes and CCC-ESF-1 fibroblasts was measured using an MTT assay.Five 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 oil.Secondary 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 oil.Results: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 Azone.Conclusions:Mint oil at proper concentration could effectively facilitate percutaneous penetration of both lipophilic and hydrophilic drugs,and exhibit higher efficiency for moderate hydrophilic drugs.Mechanisms of penetration enhancement by mint oil could be explained with saturation solubility,SC/vehicle partition coefficient and the secondary structure change of SC.

Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells.Herein,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)models.Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen secretion.Besides,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating them.As a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

二氧化碳在致密储层基质中的作用距离研究

致密油衰竭开采过程中压力、产量下降较快,补充地层能量是提高原油采收率的必要措施。CO_(2)是常用补能介质之一(CO_(2)吞吐、前置蓄能),CO_(2)增产效果与其在储层中的作用距离息息相关,针对该问题从实验和数值模拟两方面开展了CO_(2)在致密储层基质中的作用距离研究。CO_(2)传质包括对流和扩散两种方式,首先采用高温高压反应釜和致密储层岩心进行CO_(2)扩散实验,结合Fick径向扩散模型,测得了CO_(2)在致密岩心中的扩散系数;然后采用CMG软件进行CO_(2)对流、扩散建模,基于模型进行广泛的数值模拟,分析渗透率、扩散系数、驱替时间对CO_(2)作用距离的影响。研究表明,扩散系数与渗透率有关,在目标储层岩心渗透率级别下,扩散系数在10^(-10)~10^(-8)m^(2)/s范围;CO_(2)作用距离取决于对流和扩散作用,扩散作用对CO_(2)作用距离影响明显,渗透率越低,扩散作用影响越明显,渗透率越高,对流作用越主导;渗透率是CO_(2)在基质中作用距离的决定性因素;CO_(2)在致密储层基质中的作用距离较小,60d的作用距离不到10m。

柱状聚能药管聚能罩角度对煤层爆破增透效果试验研究

为解决传统预裂爆破煤体裂隙无序扩展导致增透效果不佳的问题,开展了聚能爆破药管不同聚能罩张开角度对煤层增透效果影响研究。通过建立聚能罩微元闭合理论模型,分析了随着聚能罩角度减少时形成聚能射流的速度和质量变化;以此为基础对聚能爆破增透机制进行了分析。在实验室搭建了可从煤体宏观裂纹和应变数据多角度对试验模型进行分析的双向加载气固耦合爆破相似模拟试验系统,对含瓦斯煤体试块进行普通爆破和不同聚能张开角爆破模拟对比试验。结果表明,使用聚能药包相较于普通爆破能够有效引导裂纹在聚能罩开口方向上定向发育;随着聚能罩角度减少,聚能爆破后形成的裂纹在聚能方向上更加平滑,裂纹宽度也随之增加,试块剖面更加平整;根据超动态应变仪反演结果,1号测点60°、80°和100°聚能爆破的压应力峰值分别为普通爆破的1.52倍,1.26倍和1.08倍,且60°聚能爆破到达应力峰值的时间最短,表明随着聚能罩开口的减小,聚能方向上能量集中现象越明显。通过ANSYS/LS-DYNA软件对4种不同角度的聚能爆破进行对比分析。模拟结果中60°聚能爆破初始形成的聚能射流有效应力最大,聚能方向产生的裂纹最长。试验和模拟结果表明通过使用60°聚能药包可得到更好的爆破效果,研究成果对松软高瓦斯煤层聚能爆破增透有一定的参考意义。

Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of tumor.Such barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability.To achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing nanomedicine.All these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were included.With the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

活性PELE侵彻钢筋混凝土毁伤效应仿真研究

为研究活性横向效应增强弹(Penetrator with Enhanced Lateral Effect, PELE)对钢筋混凝土靶的冲击爆燃毁伤效应,采用有限元分析软件对活性PELE毁伤钢筋混凝土靶作用行为进行数值仿真研究。基于点火增长模型,建立可描述活性芯体冲击反应过程的数值仿真模型,并根据弹道驱动试验结果对数值仿真模型进行有效性校验,计算结果与试验结果吻合较好。在此基础上开展不同冲击速度和壳体厚度条件下活性PELE对钢筋混凝土靶的毁伤特性研究。研究结果表明,随着冲击速度的提高和壳体厚度的增加,混凝土靶通孔尺寸呈先增大后减小的趋势,而对于崩落尺寸,弹丸的冲击速度则是主要影响因素。

中药挥发油透皮促渗苷类成分效果与经皮水分散失量的相关性研究

目的研究中药挥发油透皮促渗苷类成分效果与对经皮水分散失量(Transepidermal water loss,TEWL)的相关性。方法采用HPLC法测定3种苷类成分(栀子苷、龙胆苦苷、芍药苷)的含量及油水分配系数,采用改良Franz扩散池法以离体SD大鼠腹部皮肤为透皮吸收屏障进行体外透皮实验,考察高良姜、干姜、薄荷、胡椒和吴茱萸5种中药挥发油对3种苷类成分的体外透皮促渗效果,采用经皮水分散失量评价5种中药挥发油对大鼠皮肤屏障功能的影响,通过相关性分析考察中药挥发油透皮促渗苷类成分效果与其对皮肤屏障功能影响之间的相关性。结果高良姜油、干姜油、薄荷油、胡椒油能促进3种苷类成分的透皮吸收,也能显著降低大鼠的皮肤屏障功能,相关性分析结果表明中药挥发油对苷类成分的透皮促渗效果与其对皮肤经皮水分散失量的影响显著相关。结论TEWL为中药挥发油透皮促渗剂的快速筛选提供了一种简便快捷的在体评价方法。

探地雷达数值模拟与道路裂缝图像检测的深度学习增强方法

针对路面结构内部裂缝的无损检测与智能识别需求,提出一种基于改进的YOLOv8和AutoAugment增强的探地雷达检测与图像自动识别方法.结合Gprmax数值模拟、室内模型试验及现场探地雷达测试,分析得出内部裂缝在探地雷达图像上呈现出明显的"双曲线"特征,且裂缝宽度与双曲线的幅度成正比.利用MALA探地雷达GX-750检测获取路面结构内部裂缝病害图像,经多重滤波处理后采用640×640的像素框进行截取.针对裂缝特征在探地雷达图像中尺度较小的问题,通过对最新的YOLOv8模型增加一层像素为160×160的输出层得到改进的YOLOv8模型.同时,引入SKNet注意力机制进一步增加感受野,并采用power IoU损失函数以降低模型训练的损失.针对原始图像数据集,采用AutoAugment无监督自动增强方法,通过近端策略优化的强化学习算法寻找最佳增强策略及其概率和强度,实现了探地雷达数据集的有效扩充.在扩充的数据集上进行训练与测试,结果表明改进的YOLOv8模型取得了90.7%的平均检测精度和90.1%的F1分数,相比原始YOLOv8模型分别提升了6.3%和5.9%,也大幅度超越了主流的目标检测模型.在进行图像增强后,模型的平均检测精度和F1分数分别提升了4.1%和4.6%,对各类尺度的裂缝图像检测也体现出良好的鲁棒性.在养护路段应用探地雷达图像智能识别方法的检测结果与取芯验证结果相吻合,表明提出的改进模型在实际工程应用中是可靠的.

万米深井钻柱减振增能提速方法研究

万米深井超深超长井段钻进过程中存在钻柱振动剧烈、能量传递困难、破岩效率低、钻头使用寿命短等问题,亟需开展万米深井钻柱减振与井底增能技术研究。根据超深层钻井环境的主要特征,结合近年来钻柱动力学研究结果,提出了以钻井过程中钻柱振动为能量来源提高井底钻井液射流压力的方法,在减小钻柱振动保护钻头的同时,提高钻头射流压力,实现井下增能破岩,解决井下振动强度大、井底水力能量不足的问题;并研制了井底钻柱减振增能装置,进行了现场试验。研究和试验结果表明:钻柱振动蕴含巨大的能量,该能量可以转化为破岩提速能量;设计的井底钻柱减振增能装置,可以提高钻井液射流压力,同时可以降低钻柱振动导致的安全风险,从而显著提高钻井速度。研究成果为万米深井减振提速技术开拓了新方向,为加快深部油气资源的勘探与开发提供了技术支持。

香薷挥发油对吴茱萸有效成分透皮吸收的影响

目的考察香薷挥发油对吴茱萸药效成分的促渗作用以及其促透皮吸收的能力。方法采用扩散池和大鼠离体皮肤进行体外透皮实验,以吴茱萸中多种成分作为指标,HPLC测定计算各成分累积透过量。HE染色、免疫组化染色、ATR-FTIR观察皮肤及角质层的变化,GC-MS测定挥发油给药后皮内贮存挥发油成分。结果香薷挥发油对吴茱萸中多种药效成分均具有促渗作用,与阳性药氮酮相比,香薷挥发油对金丝桃苷、吴茱萸碱、吴茱萸次碱的累积透过量更大。且香薷挥发油中倍半萜成分及含量占比最大的麝香草酚更易在皮肤中贮存,可以扰乱角质层脂质结构,促进药物的渗透。结论为透皮吸收促进剂的选择提供参考。

经皮吸收促进剂用量对压敏胶黏附性的影响

目的探讨经皮吸收促进剂(简称促透剂)用量对透皮贴剂中压敏胶黏附性的影响。方法选择Plurol■Oleique CC497为模型促透剂,两种不同内聚力聚丙烯酸酯压敏胶为模型压敏胶,制备不同促透剂用量的贴剂,测定初黏力、持黏力、180°剥离强度和流变学参数。利用调制差示扫描量热法测定压敏胶玻璃化转变温度;利用红外光谱分析促透剂与压敏胶的相互作用机制。结果随着促透剂用量的增加,两种压敏胶初黏力提高,持黏力下降,高内聚力压敏胶在高促透剂用量下黏附性能仍较好。促透剂的加入会降低压敏胶的玻璃化转变温度,增加压敏胶分子流动性。红外光谱结果显示,Plurol■Oleique CC497与压敏胶间可能发生氢键作用,破坏了压敏胶聚合物分子间的相互作用,使黏附力发生变化。结论促透剂的加入会增加压敏胶的黏附性失效风险,在高促透剂用量下,应选择高内聚力压敏胶制备透皮贴剂。

活性射流作用复合混凝土结构动态毁伤特性

为研究复合混凝土结构在活性射流侵彻与爆炸联合作用下动态毁伤行为,采用全尺寸毁伤实验和动能-化学能分段数值模拟相结合的方法,获取活性射流作用不同面层厚度复合混凝土结构动态毁伤特性。实验结果表明:在PTFE/Al活性射流侵彻-爆炸联合作用下,混凝土层出现中心侵孔、崩落、隆起、径向/环向裂纹等多种毁伤模式,随混凝土层增厚,崩落面积增大,但隆起高度与径向裂纹数量减少。基于有限元分析软件,引入改进RHT混凝土模型,结合活性射流反应特性,采用FEM-SPH算法对动能侵彻-爆炸增强毁伤行为进行分段数值模拟,结合实验和数值模拟结果,给出活性射流有效质量空间分布特性,确定动能侵彻和爆炸增强毁伤增益关系,研究表明,活性射流爆炸增强毁伤可在动能侵彻毁伤基础上,分别对侵孔直径和破坏区直径增大116%和59.7%,大幅提升对复合混凝土结构破坏效果。

基于强化学习的智能化渗透路径规划与求解优化

在大数据技术广泛应用的背景下,传统渗透测试过于依赖专家经验和人工操作的问题日益显著。自动化渗透测试旨在解决上述问题以达到更准确全面地发现系统安全漏洞的效果,而寻找最优渗透路径是自动化渗透测试中最重要的任务。然而,当前的主流研究试图在包含大量冗余路径的原始解空间中规划最优路径,导致问题的求解复杂度大幅提升;此外,当前研究对漏洞利用和正奖励获取动作的评估不够。通过剔除大量冗余渗透路径,并采取漏洞利用样本增强方法和正奖励样本增强方法,可以简化问题并优化训练过程。基于此,结合解空间转换和样本增强,提出了MASK-SALT-DQN算法,并定性和定量地分析了该方法对模型求解过程的影响,通过压缩比来衡量解空间转换给模型完成目标所带来的收益。实验表明,原始解空间中冗余解路径的比例始终保持在83%以上,证明了解空间转换的必要性。此外,在标准场景下,理论压缩比为57.2,实验压缩比与理论压缩比的误差仅为1.40%,且相比基线方法,MASK-SALT-DQN在所有实验场景下均有最优的表现,证明了其有效性和先进性。

活性横向增强弹靶后横向效应实验与数值模拟

为揭示活性横向增强弹(Penetrator with Enhanced Lateral Effect,PELE)的靶后横向增强机理,开展活性PELE冲击钢靶毁伤效应实验,在钢靶后设置效应铝靶,得到不同前置钢靶厚度条件下的穿孔毁伤情况。基于点火增长模型建立活性PELE冲击爆燃反应过程的两步仿真分析模型。综合实验和仿真对活性PELE在780 m/s速度条件下冲击6~20 mm厚度范围内钢靶的靶后横向增强效应进行讨论,从效应靶毁伤、芯体反应、波相互作用及壳体破片飞散4个方面进行深入分析。分析结果表明:仿真分析模型有效模拟了活性PELE冲击靶板的爆燃反应过程;靶板厚度对活性PELE在效应靶上的穿孔散布尺寸影响显著,随着靶板厚度的增加,活性PELE的靶后横向增强效应先增大后减小;活性芯体的爆燃反应释能使壳体最大径向速度提高了40%以上。

Enzyme-triggered deep tumor penetration of a dual-drug nanomedicine enables an enhanced cancer combination therapy

Cancer cells could be eradicated by promoting generation of excessive intracellular reactive oxygen species(ROS)via emerging nanomedicines.However,tumor heterogeneity and poor penetration of nanomedicines often lead to diverse levels of ROS production in the tumor site,and ROS at a low level promote tumor cell growth,thus diminishing the therapeutic effect of these nanomedicines.Herein,we construct an amphiphilic and block polymer-dendron conjugate-derived nanomedicine(Lap@pOEGMA-b-p(GFLG-Dendron-Ppa),GFLG-DP/Lap NPs)that incorporates a photosensitizer,Pyropheophorbide a(Ppa),for ROS therapy and Lapatinib(Lap)for molecular targeted therapy.Lap,an epidermal growth factor receptor(EGFR)inhibitor that plays a role in inhibiting cell growth and proliferation,is hypothesized to synergize with ROS therapy for effectively killing cancer cells.Our results suggest that the enzyme-sensitive polymeric conjugate,pOEGMA-b-p(GFLG-Dendron-Ppa)(GFLG-DP),releases in response to cathepsin B(CTSB)after entering the tumor tissue.Dendritic-Ppa has a strong adsorption capacity to tumor cell membranes,which promotes efficient penetration and long-term retention.Lap can also be efficiently delivered to internal tumor cells to play its role due to the increased vesicle activity.Laser irradiation of Ppa-containing tumor cells results in production of intracellular ROS that is sufficient for inducing cell apoptosis.Meanwhile,Lap efficiently inhibits proliferation of remaining viable cells even in deep tumor regions,thus generating a significant synergistic anti-tumor therapeutic effect.This novel strategy can be extended to the development of efficient membrane lipid-based therapies to effectively combat tumors.

Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.