可溶微针在经皮药物递送领域的研究进展

可溶微针是一种极具潜力的新型透皮给药技术,它具有药物递送可控性、可调节性以及自我给药的便捷性等特点,在生物医学领域具有广阔的应用前景。综述微针技术的研究进展,包括微针分类、常用材料和制备方法,重点介绍了可溶微针在小分子、多肽、蛋白和核酸等药物递送领域的研究进展,系统讨论了可溶微针在生物医学领域的发展前景,以期为更精准智能的可溶微针经皮递药系统的研发提供参考。     

难溶性多西紫杉醇的溶解微针制备及体外评价

目的:制备一种用于透皮给药的负载多西紫杉醇(DTX)的溶解微针,并进行体外评价。方法:考察不同材料及配方制备DTX溶解微针(DTX-MN),通过外观和力学性能指标对微针进行表征,测定微针针头载药量。使用猪皮肤考察微针溶解性能。剥离小鼠腹部皮肤,进行体外透皮吸收研究,初步考察DTX-MN给药后的皮肤药代动力学。结果:成功制备了针头完整、力学性能良好的DTX-MN,最佳工艺得到的微针针头载药量为(14.81±4.20)μg (n=5),微针能完整插入皮肤穿透角质层屏障,且在10 min内完全溶解。体外透皮实验显示,DTX-MN的初始透皮速率和累积透皮通量都高于药物溶液组,相比溶液组,DTX-MN在24 h后累积渗透量提高了3.27倍,其释放机制符合Fickian扩散。结论:制备的DTX-MN有良好的穿刺皮肤的性能,能够显著促进DTX的透皮递送,该类微针有望促进DTX的浅表皮肤递送,具有潜在的临床应用价值。     

可溶性聚合物微针用于药物经皮递送的研究进展

目的： 了解国内外对于可溶性聚合物微针这一新型药物递送系统的研究进展，并对其优势及存在的问题进行分析，对发展前景进行展望。方法： 通过文献调研，总结可溶性聚合物微针的材料及功能，分析可溶性微针所解决的临床用药问题，以及各微针基质材料所具有的优势与面临的挑战。结果： 本文以临床不同的用药需求为视角进行分类，介绍了聚合物材料在可溶性微针递药系统中的应用，并对其优势及面临的挑战进行总结，对发展前景进行展望。结论： 目前对于可溶性聚合物微针的研究已取得了令人瞩目的进展。然而，为实现临床转化，可溶性聚合物微针递药系统的载药能力、安全性等方面仍然需要进一步的研究。     

可溶性微针的研究进展

微针是一种新型经皮给药技术,具有无痛高效递送药物、良好的患者依从性以及便于自主给药等优势。较其他类型的微针而言,可溶性微针具有制备成本低、载药量大、应用范围广、无尖锐废弃物残留、易于控制药物释放等优点。综述可溶性微针的基质和制备方法、质量评价及其在药物递送、免疫接种等多个领域的应用,探讨可溶性微针发展中存在的问题并展望其未来的研究方向,为进一步开发、应用可溶性微针提供参考。     

微针在经皮给药领域的研究

目的:阐述微针在经皮给药领域的研究。方法:简述并分析微针的特点、研究应用、存在的问题以及今后研究的重点。结果:作为一种新型的经皮给药技术,微针可能成为一种较为理想的经皮给药载体。结论:随着研究成果逐渐走入市场,微针将会带来良好的社会效益和经济效益。     

新型经皮传递胰岛素透明质酸微针制剂的制备及性能考察

目的证明透明质酸微针制剂在药物经皮传递系统方面的应用前景。方法通过皮肤及微针的显微照片考察微针刺入皮肤的性能和在大鼠体内的溶解性能;用皮肤刺激性实验评价透明质酸微针的安全性;以人的离体皮肤为透皮释药模型,通过体外经皮通透实验考察微针对模型药物胰岛素经皮吸收的促进作用。结果微针能够均匀刺穿角质层,在皮肤表面产生与微针一致的阵列形状,在皮肤断面可观察到直至真皮层的通道;在大鼠体内使用1 h后,针体能够完全溶解,皮肤刺激性指数为1.7,属于轻度刺激性;体外经皮实验中,微针中的胰岛素能够以活性形式释放,与同剂量的溶液相比,微针对胰岛素的体外经皮吸收具有显著的促进作用,稳态通透速率达75.33×10-6U.cm-2.h-1。结论以透明质酸为基质制备的微针具有良好的皮肤刺入性、溶解性和轻度的刺激性,对于生物大分子类药物的经皮吸收有明显的促进作用,具有良好的开发前景。     

光甘草定包合物缓释微针的制备及其体内外释药性能评价

目的:制备载有光甘草定(glabridin,GLA)/羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin,HP-β-CD)包合物的可溶性微针,对其理化性质及体内外经皮释药性能进行评价.方法:通过溶液搅拌-冷冻干燥法制备GLA/HP-β-CD包合物,采用相溶解度法研究药物的包合常数和包合比,利用...     

生物可降解微针的研究进展

微针给药是一种新型的经皮给药方式,可在皮肤上创造微米级的药物运输通道,增强皮肤对药物尤其是大分子药物的渗透性,且不会到达神经分布丰富的皮肤深层组织。生物可降解微针是以生物可降解材料为基质制作出的微针,除具有一般微针的优点,其具有的生物可降解特性解决了微针一旦断裂于皮肤内难以处理这一难题。因此生物可降解微针有望成为经皮给药的理想载体。本文对生物可降解微针的特点、制作方法、基质的选择、在经皮给药系统中的应用以及存在的问题等进行了概述。     

草乌甲素可溶性微针的制备、质量评价及体外透皮性能研究

目的 为克服草乌甲素现有给药方式的不足,开展草乌甲素可溶性微针的制备工艺、质量评价及体外透皮性能研究.方法 采用分层浇筑法制备草乌甲素可溶性微针,通过正交法优选最佳处方及制备工艺,并对微针进行质量评价,如微针表观、机械强度、载药量、透皮释放等.结果 草乌甲素可溶性微针的最佳处方及制备工艺为:以35％乙醇溶液作为溶剂,0...     

吲哚美辛包合物可溶性微针的制备及体内外特性研究

目的 制备载有吲哚美辛包合物的可溶性微针,考察其体外透皮性能并进行药动学特性研究。方法 采用溶液搅拌-冷冻干燥法制备吲哚美辛/羟丙基-β-环糊精包合物,正交试验筛选最佳制备处方。通过两步法将包合物负载于可溶性微针,用Parafilm模拟皮肤测试微针穿刺能力,以改良Franz扩散池进行体外经皮释放实验。建立HPLC测定大鼠血浆中吲哚美辛的方法,评价微针用于大鼠给药的药动学特征。结果 最佳处方制备的包合物包埋率为56.84%,载药量为11.90%;微针对第3层Parafilm的刺穿率为92%;IDM-HP-β-CD微针的初始体外经皮渗透速率和单位面积渗透量显著高于IDM-HP-b-CD溶液以及IDM饱和溶液;药动学结果显示微针与市售贴片相比能快速达到较高血药浓度,减少时滞。结论 包合物可溶性微针提高了药物溶解度和载药量,快速释放并显著提高药物的生物利用度,为吲哚美辛的临床应用开发了新的途径。     

Transdermal Delivery of Human Growth Hormone Through RF-Microchannels

No HeadingPurpose. To evaluate the bioavailability and bioactivity of human growth hormone (hGH) delivered transdermally through microchannels (MCs) in the skin created by radio-frequency (RF) ablation.Methods. The creation of MCs was observed in magnified rat and guinea pig skin after staining by methylene blue. Various doses of hGH in a dry form were applied on rat or guinea pig (GP) skin after the formation of MCs. The pharmacokinetic profile of systemic hGH in both animal models was monitored for 15 h post patch application. Bioactivity of the transdermally delivered hGH was verified by measuring IGF-I levels in hypophysectomized rats.Results. The ordered array of MCs was clearly visible in the magnified rat and guinea pig skin. The MCs were very uniform in diameter and of equal separation. Creation of MCs in the outer layers of the skin enabled efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs) relative to subcutaneous (s.c.) injection with plasma profiles resembling that of s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I) were observed after transdermal delivery of hGH to hypophysectomized rats indicative of the bioactivity of the transdermally delivered hGH in vivo.Conclusions. Formation of RF-microchannels is a well-controlled process. These MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high bioavailability.     

微针经皮给药系统应用于皮肤肿瘤治疗的研究进展

经皮给药系统（TDDS）作为一种经表皮给药途径递药,近年来受到广泛关注。然而,皮肤的主要屏障角质层极大地限制了大部分药物的药效。微针（MNs）可穿透角质层,为药物经皮渗透创造瞬时微通道,从而递送药物至真皮层或皮下。同时MNs给药微创、操作简单、无痛且药物可控释放,因此在皮肤局部或全身给药具有广阔的应用前景。综述MNs的制备、分类及其应用于皮肤肿瘤治疗的最新研究进展,探讨MNs在生物医药研究领域的发展前景,为MNs经皮给药系统应用于临床提供参考。     

微针与新型经皮给药载体结合的研究进展

经皮给药系统具有给药方便、血药浓度稳定、无首过效应等优点,但皮肤的屏障作用使得药物难以透过皮肤。近年来,出现了很多新型经皮给药的药物载体,如脂质体、醇质体、囊泡等,这些能通过化学方法促进药物的经皮渗透。而微针能穿透皮肤角质层形成微孔通道,通过物理方法促进药物的渗透,将微针与新型经皮给药载体结合能显著提高药物的经皮吸收的速率。本研究对微针与新型经皮给药载体结合的最新研究进行了综述,并展望了微针辅助新型药物载体经皮给药的发展前景。     

Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment Therapy

The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA.     

电致孔技术在透皮给药中的应用

电致孔可显著提高药物的经皮吸收,有望用于多肽和蛋白质类生物大分子药物的透皮给药.本文对电致孔法的透皮促渗机制、影响因素以及安全性进行了讨论,并介绍了有关实验装置及其在透皮给药中的应用.     

Transdermal Delivery of Macromolecules Using Skin Electroporation

Purposes. (1) To evaluate the feasibility of transdermal delivery ofmacromolecules by skin electroporation. (2) To assess the influenceof the molecular weight of the permeant on transport and examinewhether there exists a cut-off value of molecular weight. (3) Tolocalize the transport pathways of the macromolecules in the skin. Methods. FITC-dextran (FD) of increasing molecular weight (4.4, 12and 38 kDa) were used as model macromolecules to study the extentof transport across hairless rats skin in vitro and to localize theirdistribution in the skin by confocal scanning laser microscopy. Results. Electroporation enhanced the transport of the macromoleculesas compared to passive diffusion. The transdermal delivery by skinelectroporation of FITC and FD 4.4 was equivalent whereas transportof higher molecular weight FD was lower but significant. FITC and FD38 were observed in the epidermis both around and in the keratinocytes. Conclusions. Transdermal and topical delivery of macromolecules ofat least 40 kDa can be achieved by skin electroporation.     

Effect of Electroporation on Transdermal lontophoretic Delivery of Luteinizing Hormone Releasing Hormone (LHRH) in Vitro

Electroporation, the creation of transient, enhanced membrane permeability using short duration (microseconds to millisecond) electrical pulses, can be used to increase transdermal drug delivery. The effect of an (electroporative) electric pulse (1000 V, = 5 msec) on the iontophoretic transport of LHRH through human skin was studied in vitro. Fluxes achieved with and without a pulse under different current densities (0- 4 mA/cm²) were compared. The results indicated that the application of a single pulse prior to iontophoresis consistently yielded higher fluxes (5—10 times the corresponding iontophoretic flux). For example, at 0.5 mA/cm² fluxes were 0.27 ± 0.08 and 1.62 ± 0.05 µg/hr/cm² without and with the pulse, respectively. At each current density studied, the LHRH flux decreased after iontophoresis, approaching pre-treatment values. The results show that electroporation can significantly and reversibly increase the flux of LHRH through human skin. These results also indicate the therapeutic utility of using electroporation for enhanced transdermal transport.     

Transdermal Drug Delivery Using Low-Frequency Sonophoresis

Purpose. Application of therapeutic ultrasound (frequency: 1–3 MHz and intensity: 0–2 W/cm²) enhances transdermal drug transport, although typically by a factor of less than 10. In this paper, we show that application of ultrasound at 20 KHz induces transdermal transport enhancements of up to 1000 times higher than those induced by therapeutic ultrasound. Methods. In vitro (human cadaver epidermis) as well as in vivo (hairless rat skin) permeation experiments were performed to assess the effect of low-frequency ultrasound on transdermal transport. Results. Application of low-frequency ultrasound (20 KHz, 125 mW/cm², 100 msec pulses applied every second) enhanced transdermal transport of several permeants, including estradiol, salicylic acid, corticosterone, sucrose, aldosterone, water, and butanol, across human cadaver skin by a factor in the range of 3 to 3000 and that of salicylic acid across hairless rat skin in vivo by a factor of up to 300. Low-frequency ultrasound did not induce a long-term loss of the barrier properties of the skin (in vitro) or damage to living skin of hairless rats. At a mechanistic level, it is hypothesized that application of low-frequency ultrasound enhances transdermal transport through aqueous channels in the SC generated by cavitation-induced bilayer disordering. Support for this hypothesis is provided using experimental and theoretical analyses of low-frequency sonophoresis. Conclusions. Low-frequency ultrasound enhances transdermal transport of drugs more effectively than that induced by therapeutic ultrasound.     

Transdermal Delivery of Metoprolol by Electroporation

Electroporation, i.e., the creation of transient pores in lipid membranes leading to increased permeability, could be used to promote transdermal drug delivery. We have evaluated metoprolol permeation through full thickness hairless rat skin in vitro following electroporation with an exponentially decaying pulse. Application of electric pulses increased metoprolol permeation as compared to diffusion through untreated skin. Raising the number of twin pulses (300 V, 3 ms; followed after 1 s by 100 V, 620 ms) from 1 to 20 increased drug transport. Single pulse (100 V, 620 ms) was as effective as twin pulse application (2200 V, 1100 V or 300 V, 3 ms; followed after 1 s by 100 V, 620 ms). In order to investigate the effect of pulse voltage on metoprolol permeation, 5 single pulses (each separated by 1 min) were applied at varying voltages from 24 to 450 V (pulse time 620 ms). A linear correlation between pulse voltage and cumulative metoprolol transported after 4 h suggested that voltage controls the quantity of drug delivered. Then, the effect of pulse time on metoprolol permeation was studied by varying pulse duration of 5 single 100 V pulses from 80 to 710 ms (each pulse also separated by 1 min). Cumulative metoprolol transported after 4 h increased linearly with the pulse time. Therefore, pulse time was also a control factor of the quantity of drug delivered but to a lesser extent than the voltage at least at 100 V. The mechanisms behind improved transdermal drug delivery by electroporation involved reversible increased skin permeability, electrophoretic movement of drug into the skin during pulse application, and drug release from the skin reservoir formed by electroporation. Thus, electroporation did occur as shown by the increased transdermal permeation, on indicator of structural skin changes and their reversibility. Electroporation has potential for enhancing transdermal drug delivery.