依诺沙星角膜透过性的研究

目的:研究依诺沙星(ENX)的角膜透过性,为其处方设计提供理论基础.方法:采用体外扩散实验考察在多种渗透促进剂条件下ENX的离体兔眼角膜透过性.结果:1%的泊洛沙姆F68和2%羟丙基-β-环糊精(HP-β-CD)分别使ENX的表观渗透系数增加1.65和2.05倍,与对照组呈现显著性差异(P<0.01),而0.5%乙二胺四乙酸二钠(EDTA)与0.05%月桂氮(艹卓)酮(Azone)未能显著增大ENX的表观渗透系数(P>0.05);所有渗透促进剂均未显著改变ENX透过角膜的滞后时间;0.05% Azone和1% F68对眼组织具有刺激性.结论:2% HP-β-CD能够显著增加ENX的表观渗透系数,且对角膜无明显刺激性.     

3味中药挥发油对磷酸川芎嗪贴剂促渗作用的比较

目的考察草果挥发油、白豆蔻挥发油、砂仁挥发油单独和组合使用对磷酸川芎嗪（ligustrazine phosphate,LP）黏胶分散型透皮贴剂在离体裸鼠皮肤的促渗作用。方法采用E 100、丁二酸等制备LP黏胶分散型透皮贴剂;采用改良的Franz扩散池进行裸鼠体外透皮吸收实验;采用HPLC法进行接受液中药物含量测定。结果加入挥发油及氮酮促渗剂的LP贴剂的12 h累积渗透量（Q12）都有所增加,质量浓度为3%草果挥发油、5%白豆蔻挥发油、7%砂仁挥发油、1.5%草果挥发油＋2.5%白豆蔻挥发油、2.5%白豆蔻挥发油＋3.5%砂仁挥发油及3%氮酮组的Q12分别是（0.972±0.121）、（0.953±0.243）、（0.876±0.138）、（0.932±0.192）、（0.667±0.171）、（0.862±0.139）mg cm-2;增渗倍数（ER）分别是1.638、1.596、1.489、1.596、1.149、1.489;与阴性对照组比较,3%草果挥发油、5%白豆蔻挥发油、1.5%草果挥发油＋2.5%白豆蔻挥发油有明显的促渗作用（P〈0.01）。结论各种质量浓度单一及组合的挥发油对贴剂中LP都具有一定促渗作用,以3%草果挥发油的促渗作用最好。     

Controlling the kinetics of interferon transgene expression for improved gene therapy

Interferon (IFN) gene based therapy has been studied for the treatment of many diseases such as viral infections, cancer and allergic diseases. Non-viral vectors, like plasmid DNA, are promising ways for delivering IFN genes, because of their low immunogenicity and toxicity compared with viral vectors. Potent therapeutic effects of IFN gene transfer will depend on the level and duration of transgene expression after in vivo administration. Therefore, controlling the kinetics of transgene expression of IFNs is a rational approach for improved gene therapy. The design and optimization of plasmid vectors, as well as their route/method of administration, is the key to obtaining high and persistent transgene expression. In this review, we aim to present experimental evidence about the relationships among the properties of plasmid vectors expressing IFNs, the kinetics of transgene expression, and therapeutic effects as well as safety issues.     

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems

Abstract

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.     

The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer

Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes to the progression of tumours into a more aggressive form of cancer. However, the specific molecular mechanisms by which EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 inhibitor was reported to selectively inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK343 (a specific inhibitor of EZH2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo. Treatment with the EZH2 inhibitor led to increased levels of the epithelial marker E‐cadherin and decreased levels of mesenchymal markers such as N‐cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides direct evidence in support of EZH2 as a therapeutic target.     

壳聚糖对甲硝唑凝胶体外促透作用研究

目的 考察壳聚糖(CS)对甲硝唑凝胶体外透皮速率的影响。方法 将1.0% CS作为吸收促进剂用于甲硝唑凝胶中,以泊洛沙姆p407为凝胶基质,以含2%氮酮的甲硝唑凝胶作为阳性对照,不含任何促渗剂的甲硝唑凝胶作为阴性对照,采用改良Franz扩散池进行大鼠体外皮肤渗透实验,反相高效液相色谱法（RP HPLC）法测定接受液中甲硝唑含量,计算累积透过量Q,得出Q t回归方程及稳态渗透速率J。结果 1.0%CS组和氮酮组J分别为2.841, 2.874 μg&#8226;（cm2） 1&#8226;h 1,两者差异无显著性(P＞0.05),而与阴性组相比均差异有显著性(均P＜0.05),其透皮吸收行为符合一级方程。结论 CS对甲硝唑凝胶的体外透皮吸收有较好的促进作用,值得进一步研究。     

Transdermal and dermal delivery of adefovir: Effects of pH and permeation enhancers

The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.     

现代中药凝胶剂的发展概况

中药凝胶剂是近年来兴起的一种药物新剂型,本文就中药凝胶剂的基质与制备工艺,渗透促进剂的应用,释放行为研究和质量控制做一概述,并对中药凝胶剂的前景进行展望。     

促进剂对复方脚癣灵搽剂中小檗碱和黄芩苷体外经皮吸收及其皮内滞留量的影响

目的研究复方脚癣灵的体外经皮渗透特征,确定最佳促进剂及浓度。方法以自制双室水平扩散池和离体鼠皮进行体外渗透实验,采用HPLC法同时测定盐酸小檗碱和黄芩苷的皮内含量。结果促进剂为丙二醇和薄荷醇,最佳质量分数均为3%时,复方脚癣灵中2种成分的皮内蓄积量有显著的提高。结论应用促进剂后,制剂中小檗碱与黄芩苷在离体鼠皮内有较强的蓄积作用。