青藤碱脂质体贴剂的经皮渗透行为研究

目的:研究青藤碱脂质体贴剂的经皮渗透行为.方法:以青藤碱脂质体贴剂与不含脂质体的普通贴剂为模型药物,分别采用离体和在体经皮渗透试验进行比较研究.结果:离体试验结果表明,脂质体贴剂的皮肤药物滞留率为21.20%,普通贴剂为5.38%;在体试验结果表明,青藤碱脂质体贴剂的皮肤药物滞留率为17.44%,普通贴剂为3.97%.结论:青藤碱脂质体能增强皮肤内的贮库效应,并能以零级均衡释放药物,从而更有效地形成对局部病灶组织的靶向.     

博莱霉素脂质体凝胶的制备和体外透皮性比较

目的：研制博莱霉素（BLM）脂质体凝胶,并对其皮肤靶向性进行体外评价。方法：采用逆相蒸发-冻融法制备BLM脂质体,再用卡渡姆940为基质制成BLM脂质体凝胶;以离心法测定BLM脂质体的包封率;以体外透皮渗透释药法,比较BLM脂质体凝胶与BLM普通凝胶的透过作用。结果：BLM脂质体平均粒径为（885．20±12．08）nm,平均包封率为（66．80±1．38）％。在24h内,BLM脂质体凝胶累积透过量（Q）及稳态透皮速率（J）与BLM普通脂质体相比,均明显提高,而在皮肤中的滞留药量也显著提高（P〈0．05）。结论：BLM脂质体凝胶在体外可显著增加BLM的透皮吸收,增加皮肤中的滞留量,值得进一步研究。     

乳酸左氧氟沙星脂质体凝胶剂经小鼠在/离体的透皮吸收

目的:研究乳酸左氧氟沙星脂质体凝胶剂的皮肤渗透性。方法:以普通凝胶剂为对照,将乳酸左氧氟沙星脂质体制备成凝胶剂并应用于小鼠皮肤,用改良的Franz扩散池研究其透皮速率,以高效液相色谱法测定接受液、皮肤、血液及其他组织中的乳酸左氧氟沙星的含量。结果:所制脂质体凝胶剂有较大的透皮速率,平均为(13.5±1.0)μg.cm-2.h-1(n=6),透皮吸收行为符合Fick’s第一定律;经皮吸收结果显示体内吸收量均较普通凝胶剂低,而皮内滞留量无论是在体还是离体均较高。结论:该制剂具有良好的局部皮肤靶向性。脂质体有促进药物进入皮肤的能力,而药物进入血循环的量并不增加。     

新型脂质体给药系统：脂质体作为控制药物透皮吸收的载体

脂质体制剂作为一种具有靶向性的药物载体，多制成注射剂，用于全身给药．但也有许多报道[1~6]，说明脂质体也可以经皮肤给药，产生局部释放作用，促进表皮及真皮的吸收，并显示了它的控制药物释放的能力，能使药物持久作用于皮肤，增加治疗指数，降低全身毒性。1980年Mezei等[1]，首先提出了脂质体携带皮质激素类药物作为局部用药的可能性，当时他建议将脂质体做为皮肤给药的载体．随后他们又提出了黄体酮类、丁卡因及局部杀虫药等制成外用脂质体。脂质体制剂能够成为皮肤给药的载体，并具有一定的控释作用，目前存在有两种观点来解释脂质…     

皮肤外用药物脂质体制剂的研究进展

自从Baangham在制备生物膜模型的过程中研制出脂质体后,脂质体作为一种新型的药物载体在药学领域的研究得到了迅速的发展,在皮肤外用药物脂质体制剂的研究方面,也获得了很大的成功。脂质体外用制剂与传统的乳剂、搽剂、软膏相比,具有增效、缩短疗程和降低毒副作用的特点。1988年瑞士Cilag公司成功上市了益康哩脂质体凝胶（Pevaryl）[1],日本绿十字公司和吉富公司也上市地塞米松脂质体（Limethaone）[2],仅1980～1989年十年间,美国、日本、法国、德国和欧洲共同体就有14个脂质体药物外用制剂获得了专利[3]。由此可见,开发皮肤局部…     

咪喹莫特固体脂质纳米粒的制备及体外透皮作用

考察了以Precirol ATO5为脂质材料制备的咪喹莫特固体脂质纳米粒（SLN）的理化性质。载药SLN粒径88．3～112．8nm，多分散指数0．061～0．288，ζ电位-0．72～3．13mV，包封率50．2％～52．5％。分别考察了自制咪喹莫特乳膏及其SLN的体外透皮情况。结果表明，两者8h累积透皮量无显著性差异，持续透皮24h，SLN在局部皮肤中的药物滞留量为乳膏的1．55倍。     

酮洛芬脂质体凝胶在大鼠体内的药物动力学及皮肤组织分布研究

目的：研究酮洛芬（KPF）脂质体凝胶在大鼠体内的药物动力学及其皮肤局部组织分布。方法：选择SD大鼠为动物模型,与KPF口服给药相对照,研究KPF脂质体凝胶局部用药后在血浆和皮肤中的体内药动学行为。结果：KPF脂质体凝胶大鼠局部给药后的血药浓度Cmax、AUC0→24分别为（1．255±0．54）μg·ml^-1和（59．388±3．76）μg·ml^-1·h,局部皮肤组织的Cmax、AUC0→24分别为（28．019±1．98）μg·ml^-1和（602．21±2．84）μg·ml^-1·h。与口服KPF相比,KPF脂质体凝胶降低了血液中的分布,而具有明显的皮肤蓄积能力（P〈0．05）。结论：KPF脂质体凝胶局部给药在获得较高的皮肤组织浓度的同时,避免了较高的血药浓度的不良反应,疗效优于口服．     

挤压器联动装置制备两性霉素B脂质体

目的考察挤压器联动装置制备两性霉素B脂质体制剂的稳定性。方法使用联动装置制备两性霉素B脂质体,用透析法检测两性霉素B脂质体的药物包封率,粒径仪器跟踪脂质体制剂的粒径及其分布,测定稳定性、泄漏率及毒性。结果所用联动装置可使脂质体的制备工艺简化,投料成品一步完成,同时可在线监控粒径。采用此装置制备的两性霉素B脂质体的粒径显著小于手动方式所制备,且粒径分布较窄;药物包封率为97．3％。通过与手动方法制备的脂质体制剂的多项技术指标对比,表明采用联动装置制备的两性霉素B脂质体制剂的药物包封率高,制剂稳定性好,药物渗漏率低。结论挤压器联动装置可用于工业化生产两性霉素B脂质体制剂的产品质量稳定、可控。     

脂质体包封率的测定方法

脂质体系指将药物包封于类脂质双分子层内而形成的微型泡囊。脂质体的包封率是包封于脂质体中的药物量占脂质体系中药物总量的百分比。也有人用测定包封体积来表征脂质体的包封特性。包封率是评价脂质体制剂质量好坏的最重要的指标之一,也是脂质体能否发挥较普通制剂高效、低毒特点的关键。因此,研究脂质体时,包封率是一个重要的考察项目。     

盐酸特比萘芬醇类脂泡囊凝胶离体和在体透皮特点研究

目的:研究盐酸特比萘芬醇类脂泡囊凝胶在体和离体透皮特点。方法:采用Franz扩散池进行体外透皮实验,考察盐酸特比萘芬醇类脂泡囊凝胶、脂质体凝胶和普通凝胶经皮渗透性和皮肤滞留量;以小鼠为实验动物,3种凝胶腹部经皮给药,考察盐酸特比萘芬的血药浓度和皮肤滞留量,对比不同类型凝胶剂的透皮效果。结果:离体透皮扩散实验中,透皮速率排序为:脂质体凝胶>醇类脂泡囊凝胶>普通凝胶;皮肤内24 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。在体透皮吸收实验中,皮肤内6 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。3种凝胶中的盐酸特比萘芬在皮肤深层中的滞留量均远远大于角质层,醇类脂泡囊凝胶中药物在皮肤深层的滞留量远大于另外两种凝胶,而脂质体凝胶和普通凝胶在皮肤深层的滞留量无明显差异。结论:醇类脂泡囊对盐酸特比萘芬透皮吸收具有一定的促进作用,同时也能显著提高盐酸特比萘芬在皮肤内特别是皮肤深层中的滞留量,为治疗深部皮肤真菌感染提供了一种新方法。     

The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin permeability.

The barrier integrity of hairless guinea pig skin after treatment with an alpha hydroxy acid was assessed through in vivo topical application of an oil-in-water emulsion containing 5 or 10% glycolic acid at pH 3.0. The control was a commercial moisturizing lotion, pH 7.8. A dosing regimen for the glycolic acid formulations that was tolerated by the hairless guinea pigs and significantly decreased stratum corneum turnover time was determined using the dansyl chloride staining technique. Once-daily dosing of hairless guinea pig skin for 3 weeks with the glycolic acid formulations resulted in approximately a 36-39% decrease in stratum corneum turnover time compared with the control lotion. After this treatment, hairless guinea pigs were sacrificed for the in vitro measurement of the percutaneous absorption of [14C]hydroquinone and [14C]musk xylol. No significant differences in the 24-hour absorption of either test compound were found for skin treated with the control lotion or the glycolic acid formulations. There were also no significant differences found in the absorption of [3H]water through skin from the different treatment groups. Although no increase in skin penetration occurred after treatment with the glycolic acid formulations, histology revealed approximately a twofold increase in epidermal thickness. Also the number of nucleated cell layers nearly doubled in skin treated with 5% and 10% glycolic acid compared with the control lotion and untreated skin. These studies demonstrate that substantial changes in the structure of hairless guinea pig epidermis can occur without significant effect on skin permeability of two model compounds.     

Distribution of salicylic acid in human stratum corneum following topical application in vivo: a comparison of six different formulations.

Distribution of salicylic acid in human stratum corneum from treatment of six different formulations was assessed by quantitation of drug content in sequentially tape-stripped stratum corneum after a single 2-h dose was applied unoccluded to skin on the ventral forearm of four female subjects. The profile and total amounts of stratum corneum removed in 20 tape-strips varied among different types of formulations. With or without normalization by the total stratum corneum weights removed, the extent of drug delivery to the stratum corneum decreased in the following order: SA (5%) > > SAC (10%), Duofilm (16.7%) > TSSS (2%) > SAO (10%), Salic (2.5%), the percentage in parentheses indicating the salicylic acid concentration in each formulation. The greatest topical bioavailability was observed for the alcoholic solution containing glycerol (SA). The 10% collodion formulation (SAC) was found to deliver an amount of salicylic acid into the stratum corneum 2-fold greater than 10% ointment formulation (SAO). Use of absorption ointment (TSSS) also increased the uptake of salicylic acid into the stratum corneum in comparison with formulations based on simple ointment (SAO) and oil in water (o/w) cream (Salic). The partitioning of salicylic acid from collodion formulations (SAC and Duofilm) appeared to be concentration-independent. The results of this study indicate that topical bioavailability of salicylic acid in the stratum corneum varies substantially among different formulations.     

苦参素片与苦参素胶囊的药动学和生物等效性研究

目的:比较苦参素片与苦参素胶囊的人体药动学参数,评价二者的生物等效性。方法:将18名健康志愿者分为2组,分别空腹口服苦参素片(受试制剂)或苦参素胶囊(参比制剂)各600mg。于给药前、后采用高效液相色谱法测定氧化苦参碱血药浓度,计算2种制剂的药动学参数(以氧化苦参碱计)。结果:苦参素片、苦参素胶囊的药动学参数t1/2分别为(1.51±0.62)、(1.53±0.54)h,tmax分别为(1.35±0.13)、(1.29±0.13)h,Cmax分别为(730.86±101.13)、(729.58±74.35)ng.mL-1,AUC0～8分别为(2 579.1±244.4)、(2 505.7±223.5)ng.h.mL-1,AUC0～∞分别为(2 754.1±331.8)、(2 659.4±253.5)ng.h.mL-1。苦参素片的相对生物利用度为(103.7±13.3)%。结论:苦参素片、苦参素胶囊的主要药动学参数无显著差异,个体间、周期间和剂型间符合生物等效的假设,二者是生物等效制剂。     

Evaluation of in-vivo topical anti-inflammatory activity of indometacin from liposomal vesicles

The aim of this study was to evaluate the in-vivo drug release profile of indometacin-loaded liposomes into the skin. Large unilamellar vesicles (LUVs), composed of dipalmitoyl-L-alpha-phosphatidylcholine and cholesterol (9:1), were obtained using the extrusion method and then incorporated in hydrogels (LUV-A and LUV-B). The delivery of indometacin from the liposomal system was evaluated by determining its in-vivo local anti-inflammatory activity after cutaneous application of liposomal gel formulations; the anti-inflammatory activity is directly proportional to the amount of drug that actually crosses the skin. UVB-induced erythema on healthy human volunteers was chosen as the inflammatory model and the extent of erythema was monitored by the non-invasive technique of reflectance spectrophotometry. The results showed that LUV dispersions containing indometacin provided a high percentage of entrapped drug (approximately 84%). Furthermore, in-vivo findings revealed that the anti-inflammatory effect was more prolonged when indometacin was delivered from a liposomal gel formulation rather than from a gel formulation without liposomes. In particular, the indometacin-loaded gel formulation LUV-A showed a sustained effect, probably related to an interaction between LUV lipids and stratum corneum lipid structure. This interaction produces a depot in the stratum corneum that ensures sustained release of the drug to deeper skin layers.     

Feasibility of Measuring the Bioavailability of Topical Betamethasone Dipropionate in Commercial Formulations Using Drug Content in Skin and a Skin Blanching Bioassay

An in vivo technique has been developed which simultaneously compares a skin blanching bioassay with drug content in human stratum corneum following topical application of four 0.05% beta-methasone dipropionate formulations. Bioavailability of drug from commercial cream and ointment formulations was assessed by quantification of drug content in tape-stripped stratum corneum and skin blanching in the treated skin site under occluded conditions. Tape-stripping removed stratum corneum to a varying degree between individuals but was consistent (35%) within an individual with all formulations, day to day. A correlation (r = 0.9935) between the amount of drug in the treated stratum corneum normalized for surface area and the corresponding skin blanching score was observed with four 0.05% betamethasone dipropionate formulations. Increasing the amount of drug in the tape-stripped stratum corneum correlated with an increased skin blanching score. Ointment formulations delivered more drug to the skin and produced greater blanching scores than the cream formulations. Topical corticosteroid content in the treated skin site can therefore be quantified and correlates well with the resulting pharmacodynamic activity.     

氟康唑脂质体凝胶的制备及体外透皮实验（英文）

目的制备氟康唑脂质体凝胶,并研究其性质。方法以薄膜分散法制备氟康唑脂质体,透射电镜观察脂质体的形态,粒度分布仪测定粒径,透皮吸收扩散池测定脂质体凝胶的透皮吸收。结果氟康唑脂质体的包封率为47.68%。脂质体粒径均匀,平均粒径为250±8nm。氟康唑脂质体凝胶的累积透过量（25.27%）低于非脂质体凝胶（36.72%）,而脂质体凝胶的药物皮内滞留量（162±15μg·cm^-2于非脂质体凝胶（48±6μg·cm^-2结论氟康唑脂质体凝胶剂可显著提高药物的皮内滞留量,有望成为氟康唑的一种外用新剂型。     

花椒毒素在人体皮肤及角质层中的渗透动力学探讨

目的探讨花椒毒素在人体完整皮肤及其角质层中的渗透动力学特性。方法采用人体离体皮肤及从完整皮肤中分离出的角质层，在Franz-cell扩散池中进行不同浓度的花椒毒素乙醇溶液(0.1, 0.5, 2.5和5.0 mg·mL^-1)的渗透实验，均采用1.4%的人血清溶液作为接收液，用HPLC法测定各接收液的药物量和皮肤中的贮存药物量。结果花椒毒素乙醇溶液单位面积透过完整人皮肤速率随着浓度增加而增加，2.5 mg·mL^-1以上的浓度对其速率几乎无影响。在角质层中也存在同样的现象，但其单位面积透皮速率最大值提前了约6 h。而且随着给药浓度的增加，24 h后完整皮肤和角质层的药物贮存量也相应增加，但达到一定浓度后存在饱和现象。且花椒毒素乙醇溶液在完整皮肤中的透皮时滞(0.82 h)明显大于在角质层中的透皮时滞(0.47 h)。结论该结果对开发花椒毒素外用制剂时浓度的选择提供了依据，并对其外用药物后照射长波段紫外光(UVA)的时间提供了参考。     

Evaluation of indomethacin percutaneous absorption from nanostructured lipid carriers (NLC): in vitro and in vivo studies

The aim of this study was the evaluation, in vitro and in vivo, of indomethacin (IND) release through the skin from nanostructured lipid carriers (NLC). NLC were prepared by ultrasonication, and were characterized in order to determine drug content, and particle size; finally the NLC were processed to hydrogels (A and B). The IND release pattern from NLC hydrogels was evaluated in vitro, to determine its percutaneous absorption through excised human skin (stratum corneum and epidermis, SCE), and in vivo. To evaluate the in vivo IND release, two methods were employed: (1) the IND topical anti-inflammatory activity was determined at different time-points after its cutaneous application; in this case, the UVB-induced erythema on healthy human volunteers, chosen as inflammatory model, was monitored by reflectance visible spectrophotometry; (2) the extent of IND absorption into human skin was performed by the tape-stripping technique. The in vitro percutaneous absorption studies showed lower fluxes of IND through SCE membranes from NLC hydrogels (A and B) in comparison to an aqueous dispersion (C) and a hydro-alcoholic gel (D) both containing free IND. The findings from the former in vivo method showed that the anti-inflammatory effect, following IND topical application, was more prolonged with IND-loaded NLC gel formulation (A) if compared to formulation C and D. The results from tape stripping technique confirmed the trend obtained by the former in vivo method and indicated that IND topical bioavailability in the stratum corneum varied substantially depending upon the formulations (A-D).     

盐酸氨酮戊酸溶液剂与水凝胶的透皮及体内转化效果评价

目的 考察盐酸氨酮戊酸溶液剂及水凝胶两种制剂的透皮及皮内转化效果的差异,为药物的临床应用提供参考。方法 通过体外透皮实验考察了盐酸氨酮戊酸的参比制剂和待测制剂的透皮效果,并测定两种制剂在活体动物皮肤中的转化产物原卟啉IX （PpIX）进行定量分析,综合比较两种制剂的潜在治疗效果的差异。结果 体外透皮实验中,凝胶制剂的在新生猪皮肤中的滞留量、单位面积累积透过量（Q）、透皮速率（Flux）、透皮时滞（TL）分别为59.90 ±28.68 mg·cm2、2135.8 ±223.5 ng/mg、12.27± 5.99 mg·cm-2·h-1和0.70±0.35 h;溶液剂分别为52.68 ± 9.95 mg·cm2、 2173.5 ± 480.8 ng/mg、13.22 ± 5.82 mg·cm-2·h-1和0.80 · 0.32 h; 体内实验中,用药4h时裸鼠单位质量皮肤中的PpIX含量分别为41.91 ± mg/cm2（溶液剂）和38.83 ± 15.70 g/cm2（水凝胶）。 结论 体外实验结果表明,两种制剂在的透皮效果及皮肤内滞留量无显著差异,在体实验中两种制剂皮肤中PpIX的含量无显著性差异。     

Influence of nanosized delivery systems with benzyl nicotinate and penetration enhancers on skin oxygenation

Many novel nanosized delivery systems have been designed for topical application of drugs since they can overcome the skin barrier and improve drug bioavailability. The increased absorption is often a consequence of a reversibly disrupted barrier function of the skin by the vehicle itself or by specific ingredients that act as penetration enhancers. This paper reports the effects of two nanosized systems (microemulsion and liposomes), in the presence and absence of penetration enhancers (PE), on the topical delivery of a lipophilic drug in vivo and compares that to classical hydrogel formulation. A vasodilator benzyl nicotinate (BN), which increases the blood flow of the skin, was incorporated into the formulations, and skin oxygenation was followed by electron paramagnetic resonance oximetry. It was found that microemulsions and liposomes (with or without PE) accelerate the rate of BN action when compared to hydrogel. However, incorporation of PE in microemulsion also improves the effectiveness of BN action. To understand why PE enhances the action of BN, its effect on the structure of the stratum corneum was investigated in vitro. The increased fluidity of the stratum corneum lipids provides an explanation for the greater penetration of BN into the skin when the drug and PE are together incorporated into the appropriate formulation.