尼美舒利醇质体的体外经皮渗透特性及皮肤刺激性

目的:考察醇质体作为尼美舒利经皮给药载体的体外渗透性及刺激性。方法:采用注入法制备尼美舒利醇质体,采用Franz扩散池和鼠皮进行体外渗透实验,HPLC测定药物浓度并计算药物稳态透皮速率、12 h累积释放量及皮内滞留量;采用小鼠皮肤红斑平均积分考察尼美舒利醇质体刺激性。结果:测得尼美舒利醇质体的稳态经皮渗透速率和12 h累积释放量分别是(16.28±1.68)μg.(cm2.h)-1,(195.38±19.89)μg/cm2,与脂质体相比提高了1.9倍(P<0.05);而醇质体的皮内滞留量为(318.67±38.57)μg/cm2,仅是脂质体的1.07倍(P>0.05)。皮肤刺激性实验显示,NIM醇质体的红斑指数与生理盐水的差异并不明显(P>0.05)。结论:尼美舒利醇质体的经皮渗透性和皮肤刺激性都优于脂质体,是一种有效的经皮给药制剂。     

醇质体在经皮给药系统中的应用研究

目的:为醇质体在经皮给药系统中的应用提供参考。方法:以"醇质体""经皮给药""醇质体制备""Ethosomes""Transdermal drug delivery""Preparation of ethosomes"等为关键词,组合查询2000年1月-2017年5月在中国知网、PubMed、Elsevier、Springer等数据库中的相关文献,对影响醇质体经皮渗透的因素和醇质体的理化性质、制备方法、经皮吸收特点以及其毒性等方面进行综述。结果与结论:共检索到相关文献342篇,其中有效文献32篇。醇质体是由磷脂、高浓度醇、水构成的新型载药体系,其中醇能使醇质体流动性增强,磷脂能使醇质体更易穿过皮肤角质层;与脂质体比较,醇质体流动性更好、粒径更小、Zeta电位更低、稳定性更高、包封率更高。醇质体的制备方法简单,常用的方法有注入法、注入-超声结合法、薄膜分散法、pH梯度法。醇质体经皮渗透速率、药物经皮渗透累积量、药物在皮肤中滞留量较其他剂型显著提高;醇质体对皮肤无毒、无刺激。现已有盐酸苯海索、补骨脂素、熊果苷、芹菜素、氯诺昔康、睾酮、红霉素、利多卡因、栀子苷等药物的醇质体应用于经皮给药中。目前关于醇质体的研究很多还只是停留在简单的制备工艺、透皮吸收等实验阶段,而关于处方组成及比例对醇质体理化性质和透皮吸收效果的影响报道较少;关于醇质体皮肤滞留量的研究,多取自透皮吸收实验结束的时间点,缺乏动态的研究;有关醇质体的透皮吸收机制研究也不足。今后应从以上几方面着手,加强醇质体的基础研究。     

甘草酸二铵脂质囊泡的体外经皮渗透研究

目的 考察不同种类的甘草酸二铵(DG)脂质囊泡的体外经皮渗透情况,并制备脂质囊泡凝胶剂。方法 分别采用非质子传递溶剂法制备磷脂复合物,薄膜分散法制备柔性脂质体,注入法制备醇质体,并测定粒径;采用改良的Franz扩散池,以离体人皮进行经皮渗透实验;HPLC测定接收液和皮肤组织中药物含量。最后,将皮肤渗透性较好的囊泡处方制备成凝胶剂,考察凝胶的经皮渗透情况。结果 DG磷脂复合物24 h累计透过量为(8.07±5.42)μg·cm^-2,其余处方透过液中均未检测到药物。24 h药物在皮肤中的累积量大小顺序为磷脂复合物>醇质体>柔性脂质体>水溶液。DG磷脂复合物凝胶透皮效果与卡波姆浓度有关,0.5%卡波姆处方的皮肤中药物滞留量为1%卡波姆处方的2.2倍,降低卡波姆的浓度不但能提高DG在表皮层的含量,而且还能使药物进一步渗透至真皮层。结论 磷脂复合物能显著促进DG在皮肤中的渗透,并增加药物在皮肤中的蓄积。采用0.5%卡波姆制备磷脂复合物凝胶具有较好的经皮渗透性。     

醇质体的研究进展

目的:了解作为经皮给药载体的醇质体的研究进展。方法:根据文献,综述了醇质体在选用药物的条件、组成、制备方法、理化特性及体外透皮吸收等方面的信息。结果与结论:有效治疗剂量小、透皮速率足够大的药物可制备成醇质体;醇质体一般组成为低分子量的醇、磷脂和水;制备方法包括注入法、注入-超声结合法、薄膜分散法和pH梯度法;其形态多为球形或近球形的多室囊泡,结构较稳定,Zeta电位一般为负值,包封效果较优;渗透速率较相应的脂质体和水醇溶液快,透皮量和皮肤中累积量也相对较高。由于其无毒性及皮肤刺激性,是皮肤透皮给药较理想的载体。     

根皮素醇质体的制备、表征及对体外透皮吸收的影响

目的：制备根皮素醇质体,考察醇质体作为根皮素经皮给药载体的可行性。方法：乙醇注入法制备根皮素醇质体。采用包封率和粒径为考察指标,正交试验优化大豆磷脂用量、胆固醇用量、乙醇体积及水浴温度。测定根皮素醇质体粒径分布、多分散指标和Zeta电位,采用Franz扩散池比较根皮素及其醇质体体外透皮特征。结果：根皮素醇质体最佳处方工艺：磷脂用量为220 mg、胆固醇用量为14 mg、乙醇体积为5 mL、水浴温度为40℃,根皮素醇质体平均包封率为（83.09±1.24）%,载药量为（4.86±0.89）%,粒径为（162.19±5.88） nm,PDI为（0.067±0.011）;Zeta电位为（-15.09±2.16） mV。根皮素以醇质体形式给药后单位累积透过量提高了3.43倍,且渗透过程符合零级动力学。结论：醇质体具有包封率高,粒径分布均匀等特点,可提高根皮素的渗透速率和经皮渗透量,值得进一步研究。     

新型药物载体-醇质体的特点及研究进展

醇质体作为一种新型脂质体,具有包封率高、变形性好、皮肤刺激性小、透皮效果佳、皮肤滞留量大、可以进行细胞内传递药物等优点,使其在经皮给药过程中更加有效.本文根据国内外文献,对醇质体的特点、透皮吸收性及在抗感染药、激素透皮给药、关节炎用药及大分子药物透皮递送等方面的应用进行综述,结果表明醇质体具有良好的应用前景和开发价值.     

槲皮素醇质体凝胶剂的研制

制备槲皮素醇质体凝胶剂并进行质量评价及其抗炎作用的研究。采用注入法制备槲皮素醇质体,再加入适量卡波姆制成凝胶剂。对槲皮素醇质体的形态、粒径、表面电位、包封率、载药量进行了考察,并研究了其抗炎作用。结果表明得到的槲皮素醇质体为类球形,粒径分布均匀,平均粒径为352.7 nm,Zeta电位为-10.78 mV,包封率为61.25%,载药量为3.05%,具有明显的抗炎作用。以上结果说明所制备的槲皮素醇质体凝胶剂性质稳定,具有良好的应用前景。     

粉防已碱纳米醇质体的制备、表征和抗关节炎疗效(英文)

本研究旨在探索醇质体用于改善粉防己碱局部给药治疗关节炎的可行性。用pH梯度法制备醇质体, 并对其粒径、形态和包封率进行表征。所制备的粉防己碱醇质体为球形, 平均粒径约为78 nm, 包封率为 (52.87±3.81)%。而粉防己碱脂质体具有较大的粒径 (99 nm) 和较高的包封率 (98.80±0.01)%。此外, 与粉防己碱脂质体相比, 粉防己碱醇质体显示出显著的体外透皮性能和抗大鼠关节炎疗效, 并与市售地塞米松软膏的疗效无显著性差异。结果表明, 醇质体有望成为粉防己碱皮肤局部给药的纳米载体。     

醇质体在经皮给药系统中的研究进展

经皮给药系统是药物透过皮肤吸收的1种给药方法,是药剂学中新型的领域。经皮给药制剂具有临床上的独特优点,首先避免了首关效应、维持恒定的血液浓度和药理效应从而可增强治疗效果,减少不良反应的发生,缓解药物释放时间带来的频繁给药等优点,但同时也有其局限性。由于皮肤对药物的吸收速度和剂量有限,因此在很大程度上限制了经皮给药的途径。因此,如何促进药物透皮吸收是经皮给药制剂研究的关键。醇质体是由磷脂、高比例乙醇和水组成的一种新型脂质体,与普通脂质体相比有着不可替代的优势,包封率高、其粒径较小,有很高的变形性,可完整渗透到皮肤深层从而提高治疗效果…。基于醇质体的独特优势,随着医学技术的发展,醇质体载体在经皮给药系统中将扮演越来你越重要的角色。现将其研究进展综述如下。     

紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究

目的制备紫杉醇纳米脂质体凝胶剂,考察其粒径、粒径分布、包封率、体外释放度及透皮特性。方法采用薄膜蒸发高压微射流法制备紫杉醇纳米脂质体,以卡波姆为凝胶基质,研制紫杉醇纳米脂质体凝胶剂,采用正交试验探索最佳工艺。用粒径测定仪测定脂质体的粒径及其粒径分布,低速-超速相结合法测定包封率,透析膜扩散法进行体外释放试验,以离体小鼠皮结合改良Franz扩散装置考察其体外透皮特性。结果紫杉醇纳米脂质体的最佳工艺:卵磷脂的含量为2%,药物与磷脂质量比为1∶30,磷脂与胆固醇的质量比为10∶1。测得的粒径为81.8 nm;粒径分布系数为0.180;平均包封率73.2%。纳米脂质体凝胶剂72 h累积释放百分率为79.04%;48 h的单位面积累积渗透量为429.68μg·cm?2。结论该制剂制备工艺简单,易于涂布,具有较高的包封率,粒径较小且分布均匀,体外释放缓慢。纳米脂质体能促进脂溶性药物紫杉醇透过皮肤。     

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。     

Permeation enhancer strategies in transdermal drug delivery

Abstract

Today, ～74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.     

微针透皮给药系统应用研究进展

微针透皮给药系统是近年来透皮给药系统研究的热点。微针透皮给药系统具有注射给药和透皮给药的双重优势,具有快速、方便、无痛等众多优点,研究表明可以显著提高药物透皮速率和吸收量,特别是在蛋白质、多肽、DNA和RNA等大分子物质的透皮制剂研究领域表现出良好的效果和应用前景,本文对微针透皮给药系统应用研究的最新进展进行了综述。随着微针加工技术、载药技术和应用研究的不断深入,微针透皮技术在临床领域将会有更广泛的应用。     

Self-delivering prodrug-nanoassemblies fabricated by disulfide bond bridged oleate prodrug of docetaxel for breast cancer therapy

Breast cancer leads to high mortality of women in the world. Docetaxel (DTX) has been widely applied as one of the first-line chemotherapeutic drugs for breast cancer therapy. However, the clinical outcome of DTX is far from satisfaction due to its poor drug delivery efficiency. Herein, a novel disulfide bond bridged oleate prodrug of DTX was designed and synthesized to construct self-delivering prodrug-based nanosystem for improved anticancer efficacy of DTX. The uniquely engineered prodrug-nanoassemblies showed redox-responsive drug release, increased cellular uptake and comparable cytotoxicity against 4T1 breast cancer cells when compared with free DTX. In vivo, oleate prodrug-based nanoparticles (NPs) demonstrated significantly prolonged systemic circulation and increased accumulation in tumor site. As a result, prodrug NPs produced a notable antitumor activity in 4T1 breast cancer xenograft in BALB/c mice. This prodrug-based self-assembly and self-delivery strategy could be utilized to improve the delivery efficiency of DTX for breast cancer treatment.     

Strategies for overcoming the stratum corneum

Transdermal drug delivery has many advantages over the oral administration of drugs. This is the reason why many researchers have extensively investigated the transdermal absorption of drugs. However, a much smaller number of drugs are marketed using this route of delivery, compared to oral dosage forms, because drug absorption across the skin is very low due to the stratum corneum (the main barrier for drug absorption across the skin). Overcoming the penetration barrier would significantly improve the development of an efficient transdermal drug delivery system. Several techniques have been developed, or are under development, to bypass the stratum corneum. Approaches that have been made to overcome the stratum corneum fit into five different categories: (i) device and formulation; (ii) modification of stratum corneum by chemical enhancers; (iii) ablation; (iv) bypassing the stratum corneum via appendages; and (v) electrically assisted methods such as iontophoresis and electroporation. Furthermore, possible combinatorial uses of several approaches have been studied. Although the safety issues of these synergistic approaches still require clarification, several combinations could be promising. Finally, there is a necessity to regulate the intradermal disposition of drugs to develop a more efficient transdermal drug delivery system after overcoming the skin barrier.     

Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

To date, only approximately 20 drugs synthesized with small molecules have been approved by the FDA for use in traditional transdermal patches (TTP) owing to the extremely low permeation rate of the skin barrier for macromolecular drugs. A novel touch-actuated microneedle array patch (TMAP) was developed for transdermal delivery of liquid macromolecular drugs. TMAP is a combination of a typical TTP and a solid microneedle array (MA). High doses of liquid drug formulations, especially heat-sensitive compounds can be easily filled and stored in the drug reservoir of TMAPs. TMAP can easily penetrate the skin and automatically retract from it to create microchannels through the stratum corneum (SC) layer using touch-actuated ‘press and release’ actions for passive permeation of liquid drugs. Comparison of subcutaneous injection, TTP, solid MA, and dissolvable MA, indicated that insulin-loaded TMAP exhibited the best hypoglycemic effect on type 1 diabetic rats. A ‘closed-loop’ permeation control was also provided for on-demand insulin delivery based on feedback of blood glucose levels (BGLs). Twenty IU-insulin-loaded TMAP maintained the type 1 diabetic rats in a normoglycemic state for approximately 11.63?h, the longest therapeutic duration among all previously reported results on microneedle-based transdermal patches. TMAP possesses excellent transdermal drug delivery capabilities.     

Transdermal delivery systems

Based on a number of revolutionary ideas in the early seventies the development of transdermal delivery systems (TDS) for systemic therapy has been receiving considerable attention, both in academia and in the pharmaceutical industry. About ten years after a number of products were successfully put on the market, it has become clear that transdermal delivery of drugs not only exhibits appealing therapeutic prospects but may also provide a viable economic basis for future activities of the pharmaceutical industry. The paper will briefly stress some of the fundamentals of transdermal delivery with respect to the skin as absorption site. The main focus will be on transdermal delivery systems, covering design of transdermal systems, manufacturing of transdermal systems, polymers and adhesives, in vitro and in vivo testing of transdermal systems, principles of delivery control, and modelling of transdermal delivery. The final section will describe the fundamental strategies for enhancing drug permeation through the skin by alteration of barrier properties, approaches for thermodynamic activity increase of drug, and the iontophoretic transdermal delivery of drugs.     

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。本文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。     

Challenges and opportunities in dermal/transdermal delivery

Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs.     

纳米药物载体在经皮给药系统中应用的研究进展

目的介绍纳米药物载体在经皮给药系统中的应用。方法查阅国内外文献共31篇,从纳米药物载体在经皮给药系统中的应用及各自的优势和不足等方面进行综述。结果纳米药物载体具有提高药物的化学稳定性、促进药物经皮吸收、控制药物释放以及定位给药等优点,在药物的经皮吸收方面具有广阔应用前景。结论纳米药物载体为药物的经皮通透提供了新的途径和方法,但是其安全性和有效性仍需进一步研究。