不同密度滚轮微针对维A酸经皮渗透的影响

目的：探讨不同密度滚轮微针对维A酸经皮渗透的影响。方法：采用改良Franz扩散池法考察体外经皮渗透特性,以裸鼠离体皮肤为屏障,对照组、192针、540针滚轮微针处理组分别于2、4、6、8、10、12 h取接收液0.2 ml,用HPLC法测定维A酸含量,计算累积渗透量,并测定皮肤内维A酸滞留量。采用激光共聚焦显微镜考察在体经皮渗透特性,405 nm激发光波长下扫描,观察维A酸在皮肤内的渗透及分布。结果：离体实验中,HPLC法以平均峰面积（A）与对照品浓度（c）作线性回归,得标准曲线方程A=170 733 c-1 534.8（r=0.999 9）,线性范围为0.01~10.00 μg/ml,回收率均＞95%。192针、540针微针处理组的维A酸累积渗透量分别是对照组的2.5和6.8倍,相应的皮肤内滞留量分别是对照组的2.5和2.8倍。在体实验中,相同力度（350~400 g）下,使用192针、540针两种密度微针处理2 h后,两种微针组药物可渗透至皮肤深度分别是60和50 μm。结论：滚轮微针能有效提高维A酸的经皮渗透量,且不同密度微针的促透作用不同。     

滚轮微针技术对黄柏提取物乳膏中盐酸小檗碱经皮渗透的促进作用

采用回流法制备黄柏提取物,再制成o/w型乳膏.用HPLC法测定盐酸小檗碱的含量.以离体裸鼠皮肤为屏障,用改良Franz扩散池法考察乳膏中盐酸小檗碱的体外透皮性能,探讨滚轮微针技术对黄柏提取物乳膏中盐酸小檗碱体外经皮渗透行为和皮肤滞留量的影响.结果显示,不用或采用微针处理组乳膏中盐酸小檗碱12h的累积渗透量为(0.161±0.008)、(0.978±0.034) mg/cm2,经皮渗透速率为(0.035±0.007)、(0.197±0.018) mg·cm-2·h-1,皮肤滞留量为(0.373±0.021)、(1.364±0.342)mg/cm2.可见,滚轮微针技术能显著提高外用黄柏提取物乳膏中盐酸小檗碱的经皮渗透量(P＜0.05),增加皮肤内药物滞留量(P＜0.05).     

改装滚轮微针用于醋酸曲安奈德经皮给药的特性试验

目的:评价改装滚轮微针用于曲安奈德经皮给药的力度可控性、释药重现性和皮肤刺激性。方法:改装市售滚轮微针;石蜡切片、HE染色法观察不同微针使用力度(2.5,5.0,7.5,10.0,12.5,15.0,17.5,20.0N)时的皮肤微孔深度,探讨改装前后其力度可控性;以离体裸鼠皮肤为屏障,Franz扩散池法考察改装前后曲安奈德经皮渗透特性;评分法测定皮肤刺激性。结果:皮肤微孔深度随微针使用力度的增加而加大,微孔深度范围由65.28~106.25μm收窄为改装后的71.53~97.92μm,其RSD范围由10.45%~19.69%显著下降至改装后的2.33%~9.21%。在相同微针使用力度下,曲安奈德的累积释药量RSD范围由改装前的34.75%~55.92%,显著下降至改装后的14.29%~29.73%。改装滚轮微针用药1 h时出现轻度皮肤刺激性,之后消失。结论:与市售滚轮微针相比,改装滚轮微针具有较好的力度可控性、释药重现性,以及较小的皮肤刺激性。     

曲安奈德经皮渗透特性研究

目的 评价曲安奈德经皮渗透的特性.方法 采用Franz扩散池法,考察药物经完整皮肤和去角质层皮肤的体外透皮能力,并采用了胶带剥离、皮肤萃取法分别获取了皮肤角质层、去角质层皮肤样本,用HPLC法测定了样本中的药物含量,考察曲安奈德在皮肤不同层的分布情况.结果 曲安奈德的24h透过量去角质层皮肤约为完整皮肤的1.6倍;8h...     

曲安奈德经皮渗透特性研究

目的评价曲安奈德经皮渗透的特性。方法采用Franz扩散池法,考察药物经完整皮肤和去角质层皮肤的体外透皮能力,并采用了胶带剥离、皮肤萃取法分别获取了皮肤角质层、去角质层皮肤样本,用HPLC法测定了样本中的药物含量,考察曲安奈德在皮肤不同层的分布情况。结果曲安奈德的24 h透过量去角质层皮肤约为完整皮肤的1.6倍;8 h透皮实验,高、中、低3个浓度角质层中药物含量基本相同,真皮层则存在浓度依赖现象。结论角质层是曲安奈德的透皮吸收重要屏障,但角质层对药物的储留有饱和现象,临床上应用时需特别关注。     

两种曲安奈德新型脂质载体经皮渗透性比较

目的比较曲安奈德(TAA)纳米脂质组装体(TAA-LPPs)、TAA乙醇脂质体(TAA-Ethosomes)的体外透皮特性。方法制备TAA-LPPs和TAA-Ethosomes,采用透射电镜观察其形态,激光粒度仪测定其粒径分布,改良Franz单室扩散池进行离体大鼠皮肤渗透实验,测定两种曲安奈德脂质载体的累积透过量及在皮肤内的滞留量。结果 TAALPPs和TAA-Ethosomes均呈球形或类球形,平均粒径分别为(99.9±1.3)和(105±1.4)nm。TAA-LPPs、TAA-Ethosomes和TAA-混悬液的累积透过量分别为(53.59±4.40),(87.03±4.87),(30.54±8.61)μg·(cm2)-1,32 h后皮肤内药物滞留分别为(1.02±0.13),(0.62±0.08),(0.55±0.17)μg·(cm2)-1。结论与TAA-Ethosomes比较,TAA-LPPs更利于曲安奈德经皮局部给药,减少药物全身吸收。     

姜黄素醇质体体外透皮及其稳定性研究

目的：对姜黄素醇质体体外透皮及其稳定性进行考察方法：采用透皮扩散仪进行体外透皮实验,比较姜黄素醇质体、溶液、脂质体经小鼠离体皮肤的累积渗透量及皮肤滞留量;并将姜黄素醇质体4℃条件下冷藏,考察其稳定性。结果：姜黄素醇质体12h内单位面积皮肤的累计渗透量和皮肤滞留量是其溶液（含0．5％吐温-80）的2．71倍和2．81倍;但与其脂质体无显著差异。姜黄素醇质体4℃条件下冷藏1个月,其外观、包封率、粒径及多分散指数（PDI）变化较小。结论：醇质体作为透皮给药载体能促进姜黄素的透皮吸收,并能增加皮肤中的滞留量;姜黄素醇质体具有一定的稳定性。     

曲安奈德益康唑乳膏的透皮吸收实验

摘要：目的:建立曲安奈德益康唑乳膏体外透皮扩散实验方法,测定并评价不同厂家产品的体外透皮能力。方法:采用立式改良Franz扩散池及乳猪离体皮肤对11个厂家的产品进行体外透皮扩散试验,以HPLC法测定接受液中曲安奈德与硝酸益康唑的含量和皮肤中的贮留量。结果:2个厂家产品与原研厂家产品中曲安奈德和益康唑的体外透皮吸收情况差异无统计学意义,其余厂家产品与原研相比透皮吸收情况有一定差异。结论:新建方法适用于曲安奈德益康唑乳膏的体外透皮吸收测定,为其质量评价提供了依据。     

不锈钢微针经皮给药的研究

目的：将不锈钢微针阵列应用于经皮给药。考察离体大鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后，模型药物鬼臼毒素经大鼠皮肤的透皮能力。方法：微针预处理大鼠皮肤后，用改进的Franz扩散池研究鬼臼毒素对皮肤的透皮速率。高效液相色谱法测定鬼臼毒素的含量。结果：皮肤经微针预处理后进行鬼臼毒素透皮，其透皮速率比未经微针处理时有明显提高。三角形微针、梯形微针、矛形微针对鬼臼毒素的促渗能力依次增强；三者所引起的鬼臼毒素在皮肤中的滞留量有显著差异。同种针形微针预处理皮肤时间越长，鬼臼毒素的透皮速率越大；但微针预处理时间对皮肤中的药物滞留量无显著影响。结论：微针用于药物经皮给药时，微针针形、微针的预处理时间对药物的经皮渗透具有重要影响。     

乙肝疫苗体外经大鼠皮肤渗透与离子导入给药特性研究(英文)

对乙肝疫苗进行体外经皮实验以评价疫苗在被动扩散和离子导入情况下的经皮渗透特性。体外透皮研究采用Franz扩散池,以SD大鼠的腹部皮肤为渗透屏障,以酶联免疫法测定药物累积渗透量和在皮肤中的滞留量。乙肝疫苗(质量浓度为23μg·mL-1与46μg·mL-1)经完整皮肤被动扩散的经皮渗透量与皮肤滞留量均极少,24 h累积渗透量仅(2.1±0.1)ng.cm-2和(2.3±0.1)ng.cm-2。去除角质层后,经皮渗透量与皮肤滞留量分别提高至(383.7±86.2)ng.cm-2和(16.8±4.6)ng.cm-2,是完整皮肤的171.6倍与2.1倍(46μg·mL-1)。离子导入对于乙肝疫苗具有明显的经皮渗透促进作用:完整皮肤经皮离子导入6 h,乙肝疫苗的累积渗透量是被动扩散6 h的2.7倍(23μg·mL-1)和6.6倍(46μg·mL-1);去角质层皮肤离子导入,乙肝疫苗的累积渗透量是被动扩散6 h的1.6倍(23μg·mL-1)和1.8倍(46μg·mL-1)。离子导入也能显著增加疫苗在皮肤中的滞留量。离子导入6 h疫苗在完整皮肤中的滞留量和去角质层皮肤中的滞留量均与被动扩散24 h的皮肤滞留量接近[完整皮肤...     

Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate

The purpose of this study was to investigate solid lipid nanoparticles (SLN) hydrogel for transdermal iontophoretic drug delivery. Triamcinolone acetonide acetate (TAA), a glucocorticoids compound, was employed as the model drug. SLN containing the drug triamcinolone acetonide acetate (TAA-SLN) and their carbopol gel with stable physicochemical properties were prepared. The use of TAA-SLN carbopol gel as a vehicle for the transdermal iontophoretic delivery of TAA was evaluated in vitro using horizontal diffusion cells fitted with porcine ear skin. We found that the TAA-SLN gel possessed good stability, rheological properties, and high electric conductance. Transdermal penetration of TAA from TAA-SLN gel cross the skin tissue was significantly enhanced by iontophoresis. The enhancement of the cumulative penetration amount and the steady-state penetration flux of the penetrated drug were related to the particle size of TAA-SLN and the characteristics of the applied pulse electric current, such as density, frequency, and on/off interval ratio. These results indicated that SLN carbopol gel could be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.     

乙醇和丙二醇单用与联用对曲安奈德喷雾溶液透皮性能的影响

目的 对曲安奈德喷雾溶液进行体外透皮试验，考察乙醇和丙二醇单用与联用时对曲安奈德喷雾溶液体外透皮功能的影响。方法 选取新西兰白兔腹部皮肤，用Franz扩散池法对曲安奈德喷雾溶液进行体外透皮试验，用高效液相色谱法（HPLC）测定曲安奈德含量，用单因素方差分析法对各组间的透皮吸收速率进行对比分析。结果 乙醇和丙二醇联用时的透皮吸收速率均显著高于单用时的透皮吸收速率（P<0.05），且乙醇和丙二醇联用时对曲安奈德喷雾溶液的促透作用顺序为10%乙醇+25%丙二醇>10%乙醇+20%丙二醇>15%乙醇+25%丙二醇>15%乙醇+20%丙二醇。结论 10%乙醇和25%丙二醇联用时可使曲安奈德喷雾溶液的透皮功能达到最佳化。     

Enhancing effect of pyrrolidone derivatives on transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen

The enhancing effects of pyrrolidone derivatives on the transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen were studied by using an in vitro technique and full-thickness rat skin. The enhancers included 1-methyl (1), 1-hexyl (2), and 1-lauryl-2-pyrrolidone (3). Penetrants with various physicochemical properties were used. Flurbiprofen penetrated through skin rapidly after application alone. 5-Fluorouracil, triamcinolone acetonide, and indomethacin showed little penetration. Pyrrolidone derivatives enhanced the penetration of penetrants, especially the lipophilic compounds 2 and 3, which showed a great enhancing effect on the penetration of 5-fluorouracil and indomethacin. Pyrrolidone derivatives also enhanced the solubility of these penetrants in isopropyl myristate. Compounds 2 and 3 showed greater enhancing effects on the solubility and penetration of hydrophilic penetrants than those of lipophilic penetrants. These results suggest that the pyrrolidone derivatives enhance the flux of penetrants in skin by increasing the solubility of penetrants in the stratum corneum. Compounds 1 and 2 were detected in the receptor phase. All enhancers accumulated to a great extent in the skin. These derivatives also enhanced the skin retention of drug. It is concluded that these pyrrolidone derivatives are useful for transdermal drug delivery, although further studies are necessary before they could be used clinically.     

派瑞松乳膏中3种药物透皮特性的研究

目的:评价派瑞松乳膏中曲安奈德(TACA)、苯甲酸(BEN)、硝酸益康唑(ECN)3种药物的透皮特性.方法:采用Franz扩散池法,考察药物经完整皮肤和去角质层皮肤的体外透皮能力,并采用了胶带剥离、皮肤萃取法分别获取了皮肤角质层、去角质层皮肤样本,用HPLC法测定了样本中的药物含量.结果:经过24 h透皮吸收,TACA和BEN的去角质层皮肤渗透量分别为完整皮肤的1.5和1.3倍,ECN的渗透量基本为零.8h透皮实验,TACA高、中、低3个浓度角质层中药物含量基本相同,真皮层则存在浓度依赖现象;ECN在皮肤各层和接受室均检测不到;BEN在角质层和真皮层中的分布与TACA相似,但透过量比TACA大.结论:角质层是皮肤渗透的重要屏障,派瑞松乳膏应用于皮肤溃疡、受损或者婴幼儿皮肤仍需谨慎.     

不同促渗剂对蛇床子软膏透皮吸收特性的影响

目的考察不同促渗剂对蛇床子软膏透皮吸收的影响。方法采用改良Franz扩散池,以离体裸鼠皮肤为屏障,考察氮酮、油酸和高良姜油等不同种类的促渗剂对蛇床子软膏的累积渗透量、渗透吸收速率、增渗倍数等参数的影响。结果几种促渗剂对蛇床子软膏的透皮吸收均有较好的促进作用,其中以3%高良姜油效果最佳。结论高良姜油对蛇床子素经皮吸收具有显著的促进作用,为蛇床子经皮给药制剂处方设计和新药开发提供了依据。     

Enhanced skin penetration of P20 phosphopeptide using protein transduction domains.

Protein transduction domains (PTDs) were recently demonstrated to increase the penetration of the model peptide P20 when the PTD and P20 were covalently attached. Here, we evaluated whether non-covalently linked PTDs were capable of increasing the skin penetration of P20. Two different PTDs were studied: YARA and WLR. Porcine ear skin mounted in a Franz diffusion cell was used to assess the penetration of P20 in the stratum corneum (SC) and viable skin (VS); VS consists of dermis and epidermis without SC. The transdermal delivery of P20 was also assessed. At 1mM, YARA promoted a 2.33-fold increase in the retention of P20 in the SC but did not significantly increase the amount of P20 that reached VS. WLR significantly increased (2.88-fold) the penetration of P20 in VS. Compared to the non-attached form, the covalently linked WLR fragment was two times more effective in promoting the penetration of P20 into VS. None of the PTDs promoted transdermal delivery of P20 at 4h post-application. It was concluded that selected non-covalently linked PTDs can be used as a penetration enhancer, but greater skin penetration efficiency can be achieved by covalently binding the PTD to the therapeutic agent.     

Microneedles: a valuable physical enhancer to increase transdermal drug delivery

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery. Microneedles have been fabricated with a range of sizes, shapes, and materials. Most in vitro drug delivery studies have shown these needles to increase skin permeability to a broad range of drugs that differ in molecular size and weight. In vivo studies have demonstrated satisfactory release of oligonucleotides and insulin and the induction of immune responses from protein and DNA vaccines. Microneedles inserted into the skin of human subjects were reported to be painless. For all these reasons, microneedles are a promising technology to deliver drugs into the skin. This review presents the main findings concerning the use of microneedles in transdermal drug delivery. It also covers types of microneedles, their advantages and disadvantages, enhancement mechanisms, and trends in transdermal drug delivery.     

不同渗透促进剂对复方盐酸多塞平乳膏体外经皮的促渗作用研究

目的研究不同浓度油酸和氮酮及其复合物对复方盐酸多塞平乳膏透皮吸收的影响,提高乳膏中两种主要有效成分盐酸多塞平和醋酸曲安奈德的渗透效果.方法选用1%氮酮(aonze,AZ)、2%AZ、1%油酸(oleic acid,OA)、2%OA、1%OA-AZ 5种渗透吸收促进剂,采用离体小鼠皮为皮肤模型,在Franz扩散池上进行促渗实验.结果 5种渗透吸收促进剂对复方盐酸多塞平乳膏中盐酸多塞平促渗能力为2%AZ＞1%OA-AZ＞2%OA＞1%AZ＞1%OA;对醋酸曲安奈德促渗能力为2%AZ＞1%OA-AZ＞1%AZ＞2%OA＞1%OA.结论在所选的5种渗透促进剂中,选用2%AZ渗透促进剂对复方盐酸多塞平乳膏体外经皮促渗作用最显著,油酸、氮酮联合应用有协同作用,比单用氮酮或油酸促渗能力强.     

渗透促进剂对莫达芬尼透皮作用的影响

目的：研究10种渗透促进剂对莫达芬尼透皮吸收的影响。方法：采用改良的Franz扩散池，以40％PEG-400生理盐水溶液为接受介质，以大鼠离体腹部皮肤为透皮屏障，计算不同单元渗透促进剂作用下莫达芬尼累积渗透量Q、稳态流量Js及相关参数。结果：不同促渗剂对莫达芬尼有不同程度的促渗作用，氮酮、丁香油、月桂酸、薄荷醇对莫达芬尼促透作用比较显著，其增渗倍数分别是空白对照组的17．3850，16．3303，9．3297，8．7037倍。结论：此研究为莫达芬尼透皮吸收制剂处方的设计提供依据。