In Vitro and In Vivo Characterization of MEMS Microneedles

Transdermal drug delivery TDD systems have many advantages but are conventionally limited by the low permeability of skin. The idea of using microneedles to painlessly penetrate the topmost impermeable stratum corneum has previously been put forward. In this paper, the fabrication of solid and hollow silicon microneedles with straight side-walls and with the following dimensions: 20–100 m in diameter and 100–150 m in length is described. In vitro tests demonstrate that with prior solid microneedle application, transdermal drug transport is significantly increased by 10–20 times, with the degree of enhancement being related to needle diameter. In vivo tests in diabetic animals, however, were unable to demonstrate any delivery of insulin through the hollow microneedles. It is proposed that two factors, microneedle length and tip sharpness, have to be improved for systemic drug delivery to be seen in vivo.     

老年人急性心肌梗死82例临床分析

目的：总结老年人急性心肌梗塞（ＡＭＩ）静脉溶栓治疗经验。方法：对８２例老年人ＡＭＩ的临床资料及其中７５例的溶栓治疗资料进行分析。结果：老年人ＡＭＩ时,无胸痛史达５４．９％,入院心电图ＳＴ－Ｔ缺乏典型改变占４５．３％。经静脉溶栓治疗,梗塞动脉开通率为６２．９％,与７０岁以下ＡＭＩ组溶栓开通率比较（６５％）,无统计学差异。结论：老年人ＡＭＩ发病时,临床表现及心电图改变常不典型,应引起重视。在本文条件下     

微针的特点及其在黄褐斑治疗中的应用研究分析

黄褐斑是一种后天获得性色素沉着性疾病，困扰患者的工作和生活。外用经皮给药的主要挑战是药物透过角质层屏障的阻碍。微针作为物理促渗方法和新的递药系统，能够穿透角质层形成特定的药物输送通道，促进了药物的渗透，提高了药物的生物利用度。本文主要总结了微针的特点，并以黄褐斑为切入点，分析微针近年来在黄褐斑领域的应用研究，为后续黄褐斑微针产品的开发提供一定的参考。     

Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin

Many experiments conducted in the literature have investigated the effect of microneedles (MNs) on insulin permeation across skin. There are also a number of articles that deal with the effect of MN insertion force in skin. However, there is little known on quantifying the relationship between the effect of MN insertion force and the amount of insulin permeated for given MNs. This issue is addressed in this article. MNs of 1100 µm and 1400 µm are used to conduct in vitro permeability experiments on porcine skin, using insulin. Histological images of MN treated skin are obtained from a microtome and the viscoelastic properties of the skin sample are measured using a rheometer. An in-house insertion force device is utilized that can reproducibly apply a specified force on MNs for a set period of time using compressed air. It is deduced that when porcine skin was pretreated with an applied force of 60.5 N and 69.1 N, the resultant amount of insulin permeated was approximately 3 µg and 25 µg over a 4-hour period for the MNs used. The amount of MN force applied to porcine skin was shown to be related to the amount of insulin permeated. An increase in insertion force increase the amount of insulin permeated. It was also demonstrated that using insufficient force may have reduced or prevented the amount of insulin passing through the skin, regardless of the geometry of the MNs.     

Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin?) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1^nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 10¹⁰ ± 2.5 × 10¹⁰ and 3.8 × 10⁹ ± 1.6 × 10⁹ p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.     

微针在美容整形外科应用中的进展

微针技术近几年发展迅速,在美容整形外科应用广泛且相关种类繁多.基于这种情况,通过检索近几年国内外微针在美容整形外科应用的文献,分析了微针在皮瓣及皮片存活、瘢痕、面部年轻化、局部麻醉、脱发、皮肤松弛、痤疮、色素沉着等方面的应用现状,归纳出微针在该领域的应用的机制主要基于:微针能刺激表皮细胞和胶原的增生及微针能进行物质导入两方面.总结了微针使用过程中优点突出而不良反应较少的特点,展望了微针在美容整形外科中应用的美好前景.     

空心微针透皮给药技术的研究进展

空心微针类似于微米级的注射针,具有注射给药和透皮给药的双重特点.作为一种新型的透皮给药技术,空心微针近年来在疫苗和胰岛素等生物大分子药物的递送方面显示出极大的潜力.笔者根据近年来国内外相关的研究报道,对空心微针的促透机制、常用制备材料及工艺和在透皮给药中的应用等进行归纳总结,以期为空心微针技术的研究和发展提供参考借鉴.     

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.     

Novel Microneedle Patches for Active Insulin Delivery are Efficient in Maintaining Glycaemic Control: An Initial Comparison with Subcutaneous Administration

Purpose Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. Materials and Methods Diabetes was induced by an intravenous injection of streptozotocin (50 mg/kg bw) in adult male Sprague Dawley rats. Plasma insulin and blood glucose were measured before, during and after subcutaneous or intradermal (microneedles) infusion of insulin (0.2 IU/h) under Inactin-anaesthesia. Results Before insulin administration, all animals displayed a pronounced hyperglycaemia (19 ± 1 mM; 359 mg/dl). Administration of insulin resulted in a reduced plasma glucose independently of administration route (subcutaneous 7.5 ± 4.2, n = 9, and intradermal 11 ± 1.8, n = 9 after 240 min), but with less errors of the mean in the intradermal group. In the intradermal group, plasma insulin was increased in all latter measurements (72 ± 22, 81 ± 34, and 87 ± 20 μIU/ml), as compared to the first measurement (26 ± 13). In the subcutaneous group, plasma insulin was elevated during the last measurement (to 154 ± 3.5 μIU/ml from 21 ± 18). Conclusion This study presents a novel possibility of insulin delivery that is controllable and requires minimal training. This treatment strategy could improve compliance, and thus be beneficial for patients’ glycaemic control.     

微针对熊果苷皮肤给药的促渗作用研究

目的考察微针对熊果苷皮肤给药的促渗作用,并与化学促渗剂氮酮进行比较。方法采用深反应离子刻蚀技术制备星形硅微针。制备熊果苷水凝胶剂,采用Franz扩散池法,将人体腹部皮肤置于扩散池间,分3组:微针实验组供给室加入熊果苷水凝胶,皮肤采用微针作用;氮酮对照组供给室分别加入含有1%、3%、5%氮酮的熊果苷水凝胶,皮肤无微针作用;空白对照组供给室加入无氮酮熊果苷水凝胶,皮肤无微针作用。分别在1、3、6、12、24、36、48 h等时间点取样,以HPLC法测定接收池、皮肤表皮层和真皮层中的熊果苷含量,液相条件:C18柱(250 mm×4.6 mm,5μm);流动相为甲醇∶1×10-3mol/ml盐酸(5∶95);柱温25℃;流速1 ml/min;检测波长282 nm。求算熊果苷的累积透过量(Qr)、稳态透皮速率(Js)及皮肤累积滞留量(Qs)。结果星形硅微针可以刺穿人体皮肤角质层。HPLC标准曲线方程C=0.000 2A-0.182 9(r=0.999 9),线性范围0.4～50μg/ml、日内精密度和日间精密度分别为2.4%和2.74%,回收率均大于90%。微针作用组的熊果苷累计透过量、稳态透皮速率和表皮累计滞留量均高于5%氮酮组(P<0.01)。结论微针作用皮肤后可显著增加熊果苷皮肤渗透量。