Influence of protamine shell on nanoemulsions as a carrier for cyclosporine-A skin delivery

Novel protamine-based nanosystems have been studied for cyclosporine-A (CsA) skin delivery. Core-shell structure systems have been developed to this end. These vehicles have particles sizes of 200–300?nm, a low polydispersity index and a zeta potential which varies between ?16?mV and +35?mV. The resulting four nanosystems efficiently encapsulated CsA in their oily nucleus (60–80%) and released this drug in a controlled manner. These formulations have shown a high stability in aqueous suspension in storage conditions at 4?°C (for at least 21?months) and in acetate buffer at a physiological temperature of 37?°C (for at least 24?h). Ex vivo transdermal diffusion experiments using Franz diffusion cells and 2- to 3-day-old pig skin as a biological barrier were performed. All nanoformulations designed produced an increase in CsA transdermal delivery and two of these nanosystems presented a marked promoting effect; the more relevant parameters were smaller particle size (200?±?7?nm) and negative superficial charge. Finally, the ability of these nanosystems to enhance retention of CsA in the skin was also studied. The protamine disposition in the shell influenced CsA skin retention. Therefore, the incorporation of CsA into the nanosystems studied here makes them suitable vehicles for CsA transdermal administration.     

盐酸溴己新滴鼻剂的研制及含量测定与透皮性能评价

目的 研究盐酸溴己新滴鼻剂的制备工艺,采用HPLC法测定主药盐酸溴己新的含量并考察其体外透皮效果。方法 采用分散法制备盐酸溴己新滴鼻剂;流动相为甲醇-醋酸溶液（55：45）,流速1.0 ml/min,检测波长为247 nm,柱温30℃;以KM小鼠为模型进行体外透皮试验。结果 盐酸溴己新滴鼻剂为混悬型液体制剂,在37.44~187.2 μg/ml范围内,盐酸溴己新线性关系良好,回归方程为Y=11.996X+124.6（r=0.999 9）,低、中、高三种浓度的平均回收率分别为104.00%、101.59%、98.51%,RSD为0.89%、1.35%、0.35%（n=9）;24 h体外透皮试验累积透过率为60.29%。结论 该制剂处方合理,工艺可行,含量测定方法准确可靠。     

醇传递体在透皮给药系统中的研究进展

由于角质层的限速屏障作用,大部分药物透过皮肤的能力较差。醇传递体因能够将药物传递到皮肤深层和全身循环,且制备方法简单,使用安全而受到关注,为药物的经皮渗透提供了新的传递载体。醇传递体具有高度变形性、促进药物经皮渗透、缓释、防止药物代谢降解等优点,在药物的经皮吸收方面具有广阔的应用价值和开发前景。本文通过查阅国内外文献对醇传递体在透皮给药系统中的研究和应用等方面进行综述,为其今后在透皮领域的进一步发展提供借鉴。     

桂枝茯苓透皮贴剂主要成分含量及释放度测定

目的：测定桂枝茯苓透皮贴中芍药苷、肉桂酸、丹皮酚的含量及释放度。方法：建立HPLC法测定贴剂中肉桂酸、芍药苷和丹皮酚含量;按照《中国药典》2015年版四部溶出度与释放度测定法第四法测定贴剂的体外释放性能。结果：建立了同时测定桂枝茯苓贴中3种成分的液相色谱法。芍药苷、肉桂酸和丹皮酚的线性范围分别为16.08~144.72 μg·mL^-1,0.32~2.91 μg·mL^-1和8~72 μg·mL^-1。精密度、重复性、24 h稳定性、加样回收率良好。建立了桂枝茯苓贴剂体外释放度测定方法,贴剂释药曲线符合Higuchi方程。结论：建立的含量和释放度测定方法简便、准确,可用于桂枝茯苓透皮贴剂的质量控制。     

基于内标微透析技术同步分析尼古丁透皮贴剂在血液与皮肤的药动学

目的：利用内标微透析采样技术,同步研究尼古丁透皮贴剂的血液和皮肤局部药动学特征,获得其较全面的体内药动学规律。方法：以健康SD大鼠为实验动物,将尼古丁透皮贴剂经皮给药,磷酸可待因作为微透析采样的内标物,采集不同时间点血液和皮肤微透析样品,用高效液相色谱法（HPLC）进行测定,利用DAS 2.1药动学软件计算相关药动学参数。结果：尼古丁在血液和皮肤的平均滞留时间（MRT_0-∞）分别为（16 986.00±486.00）min和（1 597.00±851.00）min,药时曲线下面积（AUC_0-∞）分别为（19 235.42±1 801.92）mg·mL^-1·min和（56 328.82±24 900.42）mg·mL^-1·min,达峰浓度（C_max）分别为（2.00±0.50）mg·L^-1和（32.00±5.00）mg·L^-1,达峰时间（t_max）分别为（325±200）min和（570±106）min。尼古丁在血液与皮肤的药动学参数相比,AUC_0-∞、C_max、t_max在皮肤中较大,MRT_0-∞在血液中较大。结论：尼古丁透皮贴剂经皮给药后,在血液与皮肤的药动学规律存在明显的差异与联系,药动学参数证明尼古丁通过透皮渗透在皮肤中以相对较高的浓度蓄积,能达到快速、有效的吸收,进入血液后血药浓度相对较低且维持稳定,发挥显著长效作用。     

Dynamic detection of non‐protein‐bound strychnine and brucine in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches

Semen Strychni, a known toxic drug in Chinese pharmacopoeia, is notable for its therapeutic effects on local muscle and joint pain. However, oral administration can be risky. Topically administered drugs accumulate in the topical muscles and knee joints without any major increase in plasma levels; only non‐protein‐bound drugs in the biological fluids of target tissues are effective for therapeutic effects. A sensitive and rapid ultra performance liquid chromatography ‐ mass spectrometry (UPLC‐MS) method coupled with a microdialysis technique was developed to determine the non‐protein‐bound strychnine (Str) and brucine (Bru) in rabbit muscle and synovial fluid microdialysate. The UPLC separation was carried out using a 1.7μm BEH C18 column (50 mm × 2.1 mm) with a mobile phase consisting of methanol: water (29.5:70.5, v/v) with 0.1% formic acid and 20 mM ammonium acetate in water. The method was validated at concentrations ranging from 0.58 ng/ml to 467.20 ng/ml for Str and from 0.42 ng/ml to 422.40 ng/ml for Bru. Intra‐day and inter‐day accuracy ranged from 99.1% to 103.2% for Str and from 95.8% to 108.8% for Bru with intra‐day and inter‐day precision within 9.7%. The proposed method was successfully applied to determine non‐protein‐bound Str and Bru, and the analysates concentration remained stable in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches, which indicated that total Strychnos alkaloid patches could substitute for the traditional oral administration of Semen Strychni. Copyright © 2013 John Wiley & Sons, Ltd.     

长效与标准非麦角类多巴胺受体激动剂治疗帕金森病的Meta分析

目的运用Meta分析的方法,系统评价长效非麦角类多巴胺受体激动剂（NEDA）与标准NEDA在帕金森病（PD）中的有效性、耐受性和安全性。 方法制定检索策略后,检索PubMed,EMBASE,Cochrane图书馆和Web of Knowledge等数据库,同时进行参考文献的追溯和手工检索（截至2019年8月15日）。按照纳入标准和排除标准进行文献筛选,然后进行文献质量评价和数据提取。采用权重均数差（WMD）、相对危险度（RR）以及95%CI作为统计量,运用Cochrane协作网提供的RevMan 5.3软件和Stata 12.0对数据进行分析。 结果（1）共纳入11个随机对照研究,共3280例患者。（2）Meta分析结果如下。有效性方面：长效NEDA与标准NEDA间在减少UPDRS Ⅱ部分评分（WMD=-0.15,95%CI：-0.63~0.33）,Ⅲ部分评分（WMD=0.04,95%CI：-0.24~0.33）和UPDRS Ⅱ＋Ⅲ部分总和评分（WMD=0.12,95%CI：-1.25~1.49）上差异均无统计学意义（P>0.05）。耐受性方面：两种制剂在总的退出人数（RR=1.11,95%CI：0.95~1.31）、因为不良事件退出的人数（RR=1.14,95%CI：0.90~1.45）上,差异无统计学意义（P>0.05）。安全性方面：两种制剂在总的不良事件的发生风险（RR=1.02,95%CI：0.97~1.07）和严重不良事件（RR=0.96,95%CI：0.73~1.26）的发生风险上,差异均无统计学意义（P>0.05）。 结论对PD患者,长效NEDA与标准NEDA在有效性、耐受性和安全性上相似。     

The Right Stuff

Use of the percutaneous route may avoid some of the undesirable side effects that occur following oral administration in estrogen replacement therapy. At present, knowledge of estradiol transdermal properties relating to delivery of drugs in the skin is lacking. One reason is that in the existing transport models of estradiol, the skin is regarded as a single layer. This study revealed a significant difference of effects on estradiol delivery in the 3 sublayers of the skin and has caused us to believe that if we can obtain information about the transfer properties of estradiol in human skin (3 sublayers), we will not only increase our understanding of the estradiol biotransport mechanism, but also benefit clinical application. Accordingly, radioactive 17β-estradiol was used to clarify the percutaneous absorption of estradiol into the 3 sublayers of the skin (stratum corneum, epidermis, and dermis) and to evaluate the effect of drugs delivered in each sublayer. Based on data thereby obtained, mathematical models were built to further obtain transport parameters (diffusivity, permeability, lag time, and partition coefficients) for the 3 layers of the skin.     

Emerging strategies for the transdermal delivery of peptide and protein drugs

Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution. Numerous approaches have been suggested for overcoming the skin’s formidable barrier function; whereas certain strategies simply act on the drug formulation or transiently increase the skin permeability, others are designed to bypass or even remove the outermost skin layer. This article reviews the technologies currently under investigation, ranging from those in their early-stage of development, such as laser-assisted delivery to others, where feasibility has already been demonstrated, such as microneedle systems, and finally more mature techniques that have already led to commercialisation (e.g., velocity-based technologies). The principles, mechanisms involved, potential applications, limitations and safety considerations are discussed for each approach, and the most advanced devices in each field are described.     

药物结合经皮给药治疗仪治疗小儿遗尿30例疗效观察

目的:观察药物结合经皮给药治疗仪治疗小儿遗尿的疗效.方法:将50例确诊患儿随机分为2组,对照组给予口服谷维素和六味地黄软胶囊,治疗组在对照组治疗的基础上加物理疗法,采用河南三浪医疗新技术有限公司产品经皮给药治疗仪,使用遗尿专用贴片治疗,每日1次.1个疗程结束并随访1周后进行疗效统计.结果:治疗组治愈17例,有效11例,总有效率为93.3%,对照组治愈3例,有效8例,总有效率为55.0%,2组患儿总有效率经统计学分析,差异有统计意义(P＜0.05).结论:药物结合经皮给药治疗仪治疗小儿遗尿疗效显著.