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Article(id=1248601468194939019, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1248601466106172220, articleNumber=1001-2494(2024)06-0486-05, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1687708800000, receivedDateStr=2023-06-26, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1775619387911, onlineDateStr=2026-04-08, pubDate=1711036800000, pubDateStr=2024-03-22, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1775619387911, onlineIssueDateStr=2026-04-08, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1775619387911, creator=13701087609, updateTime=1775619387911, updator=13701087609, issue=Issue{id=1248601466106172220, tenantId=1146029695717560320, journalId=1190317699101192196, year='2024', volume='59', issue='6', pageStart='469', pageEnd='558', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1775619387412, creator=13701087609, updateTime=1775619937245, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1248603772348420655, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1248601466106172220, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1248603772348420656, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1248601466106172220, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=486, endPage=490, ext={EN=ArticleExt(id=1248601468475957397, articleId=1248601468194939019, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=Advances in Lipid Nanodrug Delivery Systems for Transdermal Drug Delivery, columnId=1248601467007947584, journalTitle=Chinese Pharmaceutical Journal, columnName=Original article, runingTitle=null, highlight=null, articleAbstract=

Transdermal drug delivery is one of the most commonly used clinical drug delivery methods, but it has some limitations such as low skin permeability, short duration of efficacy and low bioavailability. In order to improve the clinical efficacy of drugs and increase patient compliance, the development of lipid nano drug delivery systems for transdermal drug delivery has been favored by researchers. In this paper, the lipid nano drug delivery systems used in transdermal drug delivery systems were summarized in order to provide reference for the clinical application of transdermal drug delivery preparations and the further study of lipid nano drug delivery systems.

, correspAuthors=Xinhua XIA, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Qing LU, Cheng PENG, Xiao JIANG, Xinhua XIA), CN=ArticleExt(id=1248601469402898595, articleId=1248601468194939019, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=用于经皮给药的脂质纳米给药系统研究进展, columnId=1196884516783571586, journalTitle=中国药学杂志, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

经皮给药是临床常用的给药方式之一,但存在皮肤渗透率低、药效持续时间短、生物利用率低等局限性。为提高临床疗效,增加患者依从性,应用于经皮给药的脂质纳米给药系统开发受到研究者们的青睐。笔者对用于经皮给药系统的脂质纳米给药系统进行归纳总结,以期为经皮给药制剂的临床应用与脂质纳米给药系统的进一步研究提供参考。

, correspAuthors=夏新华, authorNote=null, correspAuthorsNote=
*夏新华,男,博士,教授,博士生导师 研究方向:中药新制剂、新剂型、新技术及制剂质量标准研究 Tel:(0731)88458227
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陆青,女,硕士研究生 研究方向:中药新制剂及制剂质量标准研究

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陆青,女,硕士研究生 研究方向:中药新制剂及制剂质量标准研究

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陆青,女,硕士研究生 研究方向:中药新制剂及制剂质量标准研究

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给药系统 优点 缺点
纳米乳 稳定性好、制备过程简易、可装载亲水和亲脂性药物 低黏度特性导致难以定量给药、粒径易变化
固体脂质纳米粒 安全性高、可促进皮肤水合作用、皮肤黏附性佳、透皮速率快、可装载亲水和亲脂性药物 包封率低、载药量低
纳米结构脂质载体 包封率高、载药量高、可增加药物溶解度、可装载亲水和亲脂性药物 药物易析出、产量低
脂质体 生物相容性高、毒性低、可装载亲水和亲脂性药物 稳定性差、容易被代谢
类脂质体 稳定性好、制作成本低、易于制备、可改变角质层的膜特性、可装载亲水和亲脂性药物 生物利用度低、不易保存
传递体 具有较好的变形能力、稳定性好、包封率高、可装载亲水和亲脂性药物 制备成本高昂、稳定性差
醇质体 粒径小、可增加药物溶解度、透皮性能佳、可装载亲水和亲脂性药物 具有皮肤刺激性、稳定性差、安全性低
), ArticleFig(id=1248653097967444080, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1248601468194939019, language=CN, label=表1, caption=

不同脂质纳米给药系统的优缺点比较

, figureFileSmall=null, figureFileBig=null, tableContent=
给药系统 优点 缺点
纳米乳 稳定性好、制备过程简易、可装载亲水和亲脂性药物 低黏度特性导致难以定量给药、粒径易变化
固体脂质纳米粒 安全性高、可促进皮肤水合作用、皮肤黏附性佳、透皮速率快、可装载亲水和亲脂性药物 包封率低、载药量低
纳米结构脂质载体 包封率高、载药量高、可增加药物溶解度、可装载亲水和亲脂性药物 药物易析出、产量低
脂质体 生物相容性高、毒性低、可装载亲水和亲脂性药物 稳定性差、容易被代谢
类脂质体 稳定性好、制作成本低、易于制备、可改变角质层的膜特性、可装载亲水和亲脂性药物 生物利用度低、不易保存
传递体 具有较好的变形能力、稳定性好、包封率高、可装载亲水和亲脂性药物 制备成本高昂、稳定性差
醇质体 粒径小、可增加药物溶解度、透皮性能佳、可装载亲水和亲脂性药物 具有皮肤刺激性、稳定性差、安全性低
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用于经皮给药的脂质纳米给药系统研究进展
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陆青 1, 2 , 彭程 1 , 姜晓 1 , 夏新华 1, *
中国药学杂志 | 研究论文 2024,59(6): 486-490
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中国药学杂志 | 研究论文 2024, 59(6): 486-490
用于经皮给药的脂质纳米给药系统研究进展
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陆青1, 2, 彭程1, 姜晓1, 夏新华1, *
作者信息
  • 1 湖南中医药大学药学院, 长沙 410208
  • 2 湖南省人民医院(湖南师范大学附属第一医院), 长沙 410002

    • 陆青,女,硕士研究生 研究方向:中药新制剂及制剂质量标准研究

通讯作者:

*夏新华,男,博士,教授,博士生导师 研究方向:中药新制剂、新剂型、新技术及制剂质量标准研究 Tel:(0731)88458227
Advances in Lipid Nanodrug Delivery Systems for Transdermal Drug Delivery
Qing LU1, 2, Cheng PENG1, Xiao JIANG1, Xinhua XIA1, *
Affiliations
  • 1 College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
  • 2 Hunan Provincial People's Hospital (The First Hospital Affiliated with Hunan Normal University), Changsha 410002, China
出版时间: 2024-03-22
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摘要
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经皮给药是临床常用的给药方式之一,但存在皮肤渗透率低、药效持续时间短、生物利用率低等局限性。为提高临床疗效,增加患者依从性,应用于经皮给药的脂质纳米给药系统开发受到研究者们的青睐。笔者对用于经皮给药系统的脂质纳米给药系统进行归纳总结,以期为经皮给药制剂的临床应用与脂质纳米给药系统的进一步研究提供参考。

经皮给药  /  脂质纳米给药系统  /  脂质体  /  固体脂质纳米粒

Transdermal drug delivery is one of the most commonly used clinical drug delivery methods, but it has some limitations such as low skin permeability, short duration of efficacy and low bioavailability. In order to improve the clinical efficacy of drugs and increase patient compliance, the development of lipid nano drug delivery systems for transdermal drug delivery has been favored by researchers. In this paper, the lipid nano drug delivery systems used in transdermal drug delivery systems were summarized in order to provide reference for the clinical application of transdermal drug delivery preparations and the further study of lipid nano drug delivery systems.

transdermal administration  /  lipid nano-delivery system  /  liposome  /  solid lipid nanoparticle
陆青, 彭程, 姜晓, 夏新华. 用于经皮给药的脂质纳米给药系统研究进展. 中国药学杂志, 2024 , 59 (6) : 486 -490 .
Qing LU, Cheng PENG, Xiao JIANG, Xinhua XIA. Advances in Lipid Nanodrug Delivery Systems for Transdermal Drug Delivery[J]. Chinese Pharmaceutical Journal, 2024 , 59 (6) : 486 -490 .
正文
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皮肤作为人体的第一道屏障,发挥抵御外来入侵的主要防御作用[1],具有防止体内水分流失、阻抑外界物质入侵、调节体温等功能[2]。皮肤生理结构从外到内分为表皮层、真皮层及皮下组织[3]。根据皮肤的解剖结构,药物经皮吸收包括以下3种途径:皮肤附属器途径、细胞内途径、细胞间途径,药物通过皮肤表面与皮肤深层产生浓度差进行被动扩散,药物的渗透量取决于药物溶解度及其扩散率[4]。经皮给药作为非侵入性给药方式,具有易于给药、无首过效应、控释、安全性强等优势,是一种很有前景的给药方法,但皮肤的屏障作用阻碍了药物的输送与转运,导致传统制剂的生物利用度低,难以达到有效血药浓度,限制了其临床应用[5]。近年来,脂质纳米给药系统作为新型载体,可提高药物穿透性,增加药物透皮量,提高给药顺应性,已被证明是促进药物透皮吸收的有效策略[6]。本文概括了临床中传统经皮给药制剂的现状,并对用于经皮给药的脂质纳米给药系统特点及其研究现状进行了综述。
1 传统经皮给药制剂概况
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自1979年美国首次使用东莨菪碱贴片治疗晕动病[7],经皮给药在医学领域中提供了一种理想的治疗方式,能克服传统给药方式的弊端,通过皮肤将足够量的药物运输至血液循环中。目前已有21种经皮给药制剂获美国食品药品监督管理局(FDA)批准上市(如阿塞那平贴剂、盐酸多奈哌齐贴剂、雌二醇贴剂),另有2种新药分别处于临床试验Ⅱ、Ⅲ期,国内已上市5种经皮给药制剂,均为贴剂(如可乐定透皮贴剂、芬太尼透皮贴剂),10种制剂处于临床试验阶段。同时,研究人员已开发出多种经皮给药剂型,如膏剂、贴剂、凝胶剂及液体类制剂等,但仍存在一些局限性:①由于皮肤对药物具有一定选择性,亲水性药物及高相对分子质量药物渗透率低;②靶向性差,经皮给药后部分药物无法到达病灶,血药浓度低无法充分发挥疗效;③稳定性不佳,需频繁给药,导致患者顺应性差。针对经皮给药传统剂型的局限性,有必要进一步研究新型经皮给药系统。目前,脂质纳米给药系统因具有控制药物释放、靶向给药、可促进大分子药物经皮渗透及稳定性佳等优点,在经皮给药中具有广阔的应用前景。
2 脂质纳米给药系统在经皮给药中的应用
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经皮给药因具有避免首过效应、减少胃肠道不良反应、安全性高、便于给药等诸多优势,已成为临床中常用的给药途径[8-9]。脂质纳米载体具有较小的粒径,有利于药物透过角质层到达皮肤深层,可持续缓慢释放药物,稳定性佳,是经皮给药的首选载体[10]。目前,基于材料特性研究人员已成功设计多种脂质纳米给药系统应用于经皮给药,如纳米乳、固体脂质纳米粒、脂质体、醇质体、传递体等[11]。脂质纳米给药系统在应用中的优缺点见表1。
2.1 纳米乳(nanoemulsions,NEs)
NEs作为一种新型给药纳米载体,具有良好的热力学稳定性,且制备过程简易,主要由油相、表面活性剂、助表面活性剂及水相组成,粒径约为10~100 nm[12-13]。由于NEs粒径较小,在经皮给药中具有一定的渗透优势,而药物与油相混溶能够增加难溶性药物溶解度,提高载药量,因此,NEs是目前经皮给药系统研究的热点。Zhang等[14]通过制备木香提取物纳米乳(Aucklandiae Radix extract-nanoemulsions,ARE-NEs),考察其抗炎效果与透皮能力。体外透皮实验与药动学研究结果表明,ARE-NEs相较于木香提取溶液组,在体内外均具有更长的滞留时间以及更高的生物利用度,展现出良好的抗炎效果与透皮性能。透射电镜结果表明,ARE-NEs主要作用于皮肤角质层,可使皮肤角质层与活性表皮高度分离,屏障功能减弱,从而增加药物流动性,发挥治疗作用。但NEs的低黏度特性导致难以定量给药,临床应用受限。基于此,研究者们将其制备成NEs凝胶[15],通过水凝胶中的增稠剂改善这一现状,结果表明,研制的地奈德NEs凝胶可有效提高透皮给药效率,延长药物的作用时间,且安全性高,是一种很有前途的经皮给药系统。
2.2 固体脂质纳米粒(solid lipid nanoparticles,SLNs)
SLNs由Muller在20世纪90年代首次提出,将药物装载于固态天然或合成的类脂中,形成粒径为50~1 000 nm的固体胶粒,具有比表面积高、生物相容好、稳定性强等特点[16]。此外,SLNs能促进皮肤水合作用,利于药物渗透,具有良好的皮肤黏附性与防紫外线功能,在经皮给药领域中表现出巨大的应用前景[17]。Pervaiz等[18]研制出一种基于SLNs的新型缓释透皮贴剂,采用Franz扩散池法进行体外透皮实验,结果发现,SLNs透皮贴剂的药物滞留量高,透皮速率快,透皮效果好。皮肤刺激性试验结果提示,含有SLNs的透皮贴剂72 h内未观察到红斑迹象,而普通药物贴剂出现红斑迹象,表明SLNs透皮贴剂安全性高,无皮肤刺激性。酮洛芬是一种芳基烷酸类化合物,临床上常用酮洛芬凝胶缓解局部炎症及肢体关节各种类型的疼痛,但该药半衰期较短,仅为120 min,因此需频繁给药,导致患者顺应性差。Jagdale等[19]采用微乳法制备酮洛芬固体脂质纳米粒,包封率为74.8%,药物溶解度由0.014 8 mg·mL-1提升至0.619 4 mg·mL-1。体外释放实验表明,酮洛芬固体脂质纳米粒凝胶在透析介质中可持续缓慢释放8 h,显著延长酮洛芬的作用时间,是一种很有前途的经皮给药系统。
2.3 纳米结构脂质载体(nanostructured lipid carriers,NLCs)
NLCs是在固体脂质纳米粒的基础上进行改良的第二代脂质系统,以固液混合脂质作为载体,液态脂质的加入造成固态脂质晶格缺陷,内部空间结构增加,因此NLCs具有更高的包封率与载药量[20-21]。在经皮给药中,NLCs是一种很有前途的给药系统,可以通过不同的机制将药物穿透皮肤屏障:①在皮肤表面形成薄膜,保持皮肤水分充足,增加皮肤水合作用,促进药物的渗透;②NLCs的磷脂成分可改变皮肤脂质基质的排序,利于亲脂性分子通过,深入穿透角质层;③表面活性剂的使用可促进皮肤表面对药物的吸收[22-23]。别嘌醇(allopurinol,APL)是次黄嘌呤的同分异构体,为临床治疗痛风与高尿酸血症的一线药物。但别嘌醇溶解性差,半衰期短,易出现过敏反应,导致其临床使用率逐渐降低。Ali等[24]以NLCs包封药物,采用凝胶基质对其赋形,开发了一种新型经皮给药系统。结果表明,别嘌醇纳米结构脂质载体凝胶(APL-NLCs-Gel)包封率高达97.3%,24 h后累积释放率为53.85%,具有良好的缓释效果。体外透皮实验中,APL-NLCs-Gel累积渗透量为863 μg·cm-2,与游离ALP相比,APL-NLCs-Gel的渗透率提高了28倍。体内药效学研究表明,低剂量的APL-NLCs-Gel产生了更佳的治疗效果。这些结果揭示NLCs可持续释放药物,通过增加药物溶解度,增强药物渗透性,从而提高疗效。
2.4 脂质体(liposomes,Lips)
Lips是将药物包封于类脂质双分子层内而形成的微小囊泡,具有生物相容性和生物降解性良好、毒性较低等优势,已广泛应用于医学领域[25-27]。Lips主要由磷脂与胆固醇组成,经典的双分子层结构使得Lips既可以装载亲水性药物,也可以装载疏水性药物[28]。此外,可选择具有不同相变行为、亲水性、疏水性、电荷及刺激响应等特性的脂质,将其设计为不同物理化学特性的载体[29]。Lips作为经皮给药载体,可增加药物通过角质层的可能性,减少全身效应,克服经皮给药存在的许多障碍,引起了研究者们的密切关注[30]。Sacha等[31]通过对已上市的3种双氯芬酸钠凝胶进行对比:浓度分别为11.6、23.2 mg·g-1的普通凝胶,10 mg·g-1的Lips凝胶。结果表明,10 mg·g-1的Lips凝胶累积渗透量最高,48 h后达到(69.30±14.38)μg·cm-2,比浓度为23.2 mg·g-1普通凝胶高2倍,具有良好的透皮性。为提高白藜芦醇的渗透率及治疗效果,Lafarge等[32]将其装载于Lips中,在3 h后观察到Lips可显著增加药物在皮肤中的渗透速率,增幅为73%。Kuznetsova等[33]设计出一种阳离子Lips用于经皮给药,实验结果表明,药物的累计渗透量显著增加,并延长了药物作用时间,可长达51 h,具有良好的缓释作用。
2.5 类脂质体(niosomes,Nios)
Nios是由非离子表面活性剂、胆固醇和磷脂组成的人工囊泡,具有类似于Lips的生物膜结构,可递送亲水性及亲脂性药物[34]。相较于传统Lips,具有更高的稳定性、更低的成本、易于制备等优势[35]。此外,由于非离子表面活性剂的存在,Nios能够改变角质层的膜特性,从而提高通过生理屏障的渗透效率,促进药物传递至体循环,因此,可作为潜在的经皮给药系统[36]。在经皮给药中Nios主要通过以下3种方式传递药物:①通过囊泡膜上的配体与特定的受体结合,将药物从囊泡直接转移到皮肤深层;②通过与细胞膜融合,促进内容物与细胞质混合;③内吞作用,细胞质中存在溶酶体降解类脂质体的膜结构,从而将包封的药物释放至目标部位[37]。Wu等[38]为降低乌头碱在经皮给药中产生的毒性,使用单硬脂酸甘油酯与泊洛沙姆407制备乌头碱Nios,包封率为82.68%,同时在激光共聚焦下观察到,Nios可通过皮肤附属器途径透入皮肤,进行释放,在毛囊疾病的治疗中具有一定优势。
2.6 传递体(transfersomes,TFs)
TFs是一种具有双层结构的高弹性或超柔性的囊泡,由磷脂和边缘活化剂如Tween80或Span40组成,因边缘活化剂的加入使其具有较好的变形能力,能穿过比自身体积小数十倍的皮肤小孔而结构不被破坏[39]。边缘活化剂的类型与浓度对于TFs的理化性质有着显著影响,能够决定其稳定性及变形能力[40]。TFs在经皮给药中递送药物有以下途径[41]:①由于囊泡双分子层的高变形能力,TFs可以挤压通过角质层细胞内脂质,穿透皮肤,克服屏障功能;②边缘活化剂有助于产生跨表皮渗透梯度,导致TFs从高梯度移动到低梯度,挤压角质层,穿透皮肤屏障。Umam等[42]研制出芝麻醇TFs凝胶,用于促进伤口愈合。结果表明,芝麻醇TFs凝胶具有更高的皮肤渗透率和滞留量,对皮肤无刺激作用,能够延长体内作用时间。动物实验表明,使用芝麻醇TFs凝胶21 d后,可观察到伤口收缩,明显改善皮肤组织结构,治疗效果良好。Rasheed等[43]采用薄膜分散法制备葡萄糖胺TFs用于骨关节炎的治疗,包封率可达94.54%,稳定性良好。另有文献[44]报道,表面活性剂的浓度与TFs包封率呈负相关趋势,同时磷脂和表面活性剂浓度对TFs粒径大小有显著性影响[44]。因此,在TFs的制备中需严格考察磷脂与表面活性剂的最佳配比。
2.7 醇质体(ethosomes,ETs)
ETs是一种新型、柔软、无创的囊泡,旨在将药物传递至更深层皮肤参与体循环,由磷脂、乙醇、水组成,可通过热法和冷法两种方法制备[45]。乙醇是一种增强渗透剂,使ETs能够穿透皮肤屏障,加深透皮渗透程度,将亲水性或亲脂性药物递送至体循环[46]。此外,高浓度乙醇可增加药物溶解度,由于乙醇作为表面负电荷供体,可避免囊泡系统聚集,导致相同条件下制备的ETs相较于Lips具有更小的粒径[47]。据报道[48],磷脂与乙醇可协同发挥促渗透作用,一方面,乙醇增加脂质双分子层的流动性,降低角质层中高度有序的脂质密度,使药物可通过细胞间脂质层渗透到皮肤层深处。另一方面,ETs与角质层脂质相互融合,促进药物扩散至体循环。为增加药物溶解度,控制药物长效释放,Nasr等[49]通过热法制备缬沙坦ETs,具有较高的包封率(94.24±0.2)%,粒径为(45.8±0.5) nm。药动学实验结果表明,口服给药的药-时曲线下面积为(7.0±2.94) μg·h·mL-1,而缬沙坦ETs凝胶的药时曲线下面积(137.2±49.88)μg·h·mL-1,具有良好的透皮吸收效果。目前,ETs的应用仍存在一定局限性[50],由于乙醇具有一定刺激性,需通过体内外实验评估ETs对于完整、受伤、感染和损伤皮肤的皮肤耐受性和安全性。此外,ETs中的磷脂含量易被水解和氧化,这会导致ETs的稳定性不佳,因此需要对ETs体系的长期稳定性进行评估。
3 总结与展望
收起
角质层是阻碍药物进入深层皮肤组织的主要屏障,脂质纳米给药系统为促进药物经皮传递开辟了新的途径。脂质纳米给药系统具有给药途径多样性,有效提高临床疗效,增加患者的依从性等优势,能够提供理想的药物递送状态,解决与传统药物相关的许多科学问题,在经皮给药方面的应用已取得突破性进展,被广泛认为是治疗局部和全身疾病的下一个前沿。第一代经皮给药系统主要依赖于药物自身属性,仅能应用于低相对分子质量、亲脂性、低剂量的药物。然而,这类药物的数量和治疗功能有限。为满足临床中患者的需求,第二代经皮给药系统引入了促透增强技术,如化学促进剂和离子导入等,可增强部分亲水性药物的透皮能力。然而,这些促透技术仍然无法解决大分子药物的经皮给药问题。因此,随着微米和纳米级工艺的出现,第三代经皮给药系统利用脂质纳米给药载体具有控制药物释放、靶向给药、可促进大分子药物经皮渗透、稳定性佳等优势,使得大分子药物甚至疫苗能够穿透皮肤。目前,全球已有14个脂质纳米制剂获批上市,但多数采用静脉注射给药方式,由于经皮给药制剂相关政策完善较晚,直至2019年FDA才明确研发、生产等流程的关键参数且制备成本高昂,此外,皮肤的屏障作用也是经皮给药制剂的研发所要突破的难题。因此在经皮给药系统中的应用研究者们仍有广阔的探索空间,未来可从以下几个方面进行完善:①开发结构更加复杂的新型脂质纳米给药系统,以提高载药量;②扩大用于开发新型脂质纳米给药系统的材料范围;③结合新剂型开发高效、安全的新型脂质纳米给药系统;④大多数研究仍仅处于临床前或临床早期阶段,尚未得出明确结论,需对不同脂质纳米给药系统的皮肤穿透机制进行更深入和全面的研究。相信随着多学科理论和技术的发展,脂质纳米给药系统在经皮给药的应用中将会有更广阔的发展前景。
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2024年第59卷第6期
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  • 接收时间：2023-06-26
  • 首发时间：2026-04-08
  • 出版时间：2024-03-22
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  • 收稿日期：2023-06-26
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    1 湖南中医药大学药学院, 长沙 410208
    2 湖南省人民医院(湖南师范大学附属第一医院), 长沙 410002

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*夏新华,男,博士,教授,博士生导师 研究方向:中药新制剂、新剂型、新技术及制剂质量标准研究 Tel:(0731)88458227
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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