纳米递送系统,聚焦于亲疏水性中医药
Nanoparticle Delivery System, Focusing on Hydrophilic and Hydrophobic TCM
摘要: 目的:传统中医(TCM)在现代医学中占据着关键地位,但其应用常常受到诸如草药成分溶解度低、稳定性差以及生物利用度低等问题的阻碍。为解决这些难题,纳米粒子递送系统应运而生,展现出显著潜力,能够提升中药疗效并减少副作用。本研究旨在全面回顾纳米粒子递送系统在亲水性和疏水性中药成分中的研究与应用情况,旨在评估并优化这些技术,通过将传统医学与前沿纳米技术相结合,推动中药的现代化和国际化进程。方法:为探究纳米粒子递送系统在改善中药成分的物理化学性质方面的应用,进行了全面的文献综述。该研究重点关注了各种纳米载体,包括脂质基、聚合物、无机和杂化纳米粒子,以及它们在递送亲水性和亲脂性中药成分方面的各自优缺点。此外,还分析了具体实例,以说明这些系统如何提高中药的溶解性、稳定性、生物利用度和靶向能力。结果:该综述表明,纳米粒子递送系统有效地解决了中药成分固有的局限性。对于亲水性成分,基于聚合物的纳米乳液系统显著提高了其稳定性,并促进了靶向递送。相反,脂质基和聚合物纳米粒子被发现能显著提高疏水性成分的溶解性和生物利用度。此外,该研究还强调了这些系统通过精确控制药物释放和靶向性来降低毒性并改善治疗效果的潜力。结论:将纳米粒子递送系统与传统中药相结合,为克服传统草药医学面临的挑战提供了一种新颖的方法。通过利用纳米载体的独特特性,我们可以显著提高中药的疗效和安全性,从而为其在现代医学中的更广泛应用铺平道路。这项研究强调了在该领域持续进行研究和创新的重要性,最终目标是实现传统中药在全球医疗保健中的全部潜力。
Abstract: Objective: Traditional Chinese medicine (TCM) holds a pivotal position in the modernization of medicine, yet its application is often hindered by issues such as low solubility, instability, and poor bioavailability of herbal components. To address these challenges, nanoparticle delivery systems have emerged as a promising solution, showcasing significant potential in enhancing the efficacy and reducing side effects of TCM. This study aims to comprehensively review the research and application of nanoparticle delivery systems in both hydrophilic and hydrophobic TCM ingredients, with the objective of assessing and optimizing these technologies to facilitate the modernization and internationalization of TCM by synergizing traditional medicine with cutting-edge nanotechnology. Methods: A thorough literature review was conducted to explore the utilization of nanoparticle delivery systems in improving the physicochemical properties of TCM ingredients. The study focused on various nanocarriers, including lipid-based, polymeric, inorganic, and hybrid nanoparticles, and their respective merits and limitations in delivering hydrophilic and hydrophobic TCM components. Additionally, specific examples were analyzed to illustrate how these systems enhance the solubility, stability, bioavailability, and targeting capabilities of TCM. Results: The review revealed that nanoparticle delivery systems effectively address the inherent limitations of TCM ingredients. For hydrophilic components, polymer-based and nanoemulsion systems significantly improved their stability and facilitated targeted delivery. Conversely, lipid-based and polymeric nanoparticles were found to markedly enhance the solubility and bioavailability of hydrophobic ingredients. Furthermore, the study highlighted the potential of these systems in reducing toxicity and improving therapeutic outcomes through precise control over drug release and targeting. Conclusion: The integration of nanoparticle delivery systems with TCM offers a novel approach to overcoming the traditional challenges associated with herbal medicine. By leveraging the unique properties of nanocarriers, we can significantly enhance the efficacy and safety of TCM, thereby paving the way for its broader application in modern medicine. This study underscores the importance of continuous research and innovation in this field, with the ultimate goal of realizing the full potential of TCM in global healthcare.
文章引用:王威, 杜晓明, 段学庆, 陈福, 李荣光, 李江龙. 纳米递送系统,聚焦于亲疏水性中医药[J]. 临床医学进展, 2026, 16(2): 3263-3273. https://doi.org/10.12677/acm.2026.162739

1. 引言

中医药,作为中华民族的瑰宝,千百年来在治疗各种疾病、维护人类健康方面发挥了不可替代的作用。随着现代医学的发展,中医药的现代化和国际化进程日益加快。然而,中药在应用过程中面临诸多挑战,如活性成分的质量不可控、溶解度低、稳定性差、不良反应以及靶向性不足等,这些问题限制了中药的广泛应用和疗效发挥。因此,探索新型药物递送系统,以提高中药的生物利用度和治疗效果,成为当前中医药研究的重要方向。纳米技术作为一种前沿的药物递送手段,为中药的现代化带来了新的机遇。纳米颗粒的尺度在10~100 nm之间,与生物分子尺度相近,能够在生物体内与细胞、组织等高效相互作用,展现出高渗透性、选择性和生物稳定性等优势[1]。通过纳米颗粒递送系统,中药的有效成分、复方制剂或原药可以被封装在纳米颗粒内部,实现药物的靶向递送和控释,从而提高药物的稳定性和生物利用度,降低副作用。近年来,纳米颗粒递送系统在中医药领域的应用研究日益增多,显示出广阔的应用前景和潜力[2]。大量实验证明,纳米颗粒递送系统可以增强中药的稳定性[3]-[5],现阶段,关于纳米递送系统在中医药领域应用的综述已有不少,但大多数综述侧重于纳米技术的基本原理、制备方法以及在某些特定中药成分或疾病治疗中的应用。相比之下,本文在全面梳理纳米颗粒递送系统在亲水性和疏水性中药中的研究与应用基础上,进一步聚焦于该技术的评估与优化,旨在深入探讨纳米技术与中医药传统医学的互补性,推动中医药的现代化和国际化发展。本文的创新点在于综合分析了不同类型纳米载体的优缺点,并结合具体中药成分的特性,提出了针对性的递送策略,为纳米颗粒递送系统在中医药领域的应用提供了更为全面和深入的见解[6] [7]。尽管纳米颗粒递送系统在中医药领域展现出巨大潜力,但仍面临诸多挑战,如纳米颗粒的制备和表征技术不足、体内降解行为及安全性评估缺乏、与中药成分相互作用机制不明确等。因此,本文不仅总结了现有研究成果,还指出了未来研究的方向和重点,旨在通过进一步完善和改进纳米颗粒递送系统,使其在中医药领域发挥更大的作用,为中医药的传承与创新贡献力量。

2. 中医药领域的纳米递送系统

随着中医药现代化和国际化的不断推进,纳米技术在中药递送中的应用逐渐深入,纳米递送系统已成为解决中药成分稳定性、生物利用度和靶向性不足的有效手段。目前,中药纳米载体主要包括脂质纳米载体、聚合物纳米载体、无机纳米载体和杂化纳米载体。每种载体在药物递送中各有特色,但其应用的选择需综合考虑中药成分的理化性质、治疗需求、稳定性、生物相容性和成本(见表1)。

Table 1. Classification and characteristics of nanocarriers

1. 纳米载体的分类与特点

纳米载体

优点

不足

脂质基纳米载体

生物相容性好,生物降解性强

稳定性和药物释放控制存在问题[8]-[10]

微乳液与纳米乳液

制备简便,稳定性好

纳米乳液成本较高[11] [12]

转移体

实现精确的靶向药物输送

对需进一步研究药物–载体的相互作用[13] [14]

聚合物纳米载体

可包裹多种药物,缓释性能强

生物相容性和降解性需改善[15] [16]

无机纳米载体

具有磁性、光学等独特性质

生物相容性和长期安全性需评估[17] [18]

杂化纳米载体

结合不同材料优点,兼具多功能性

合成复杂,成本较高[19] [20]

2.1. 原理与应用

纳米颗粒递送系统通过将药物、基因或其他生物活性物质封装在纳米颗粒中,以提高药物在体内的有效性。纳米技术的应用可改善药物的溶解度、稳定性、生物利用度以及靶向性,从而提高治疗效果并减少副作用[21] [22]。在中医药领域,纳米颗粒递送系统被用于中药活性成分的递送,克服了传统给药方式的局限性,特别是在口服和注射方面的吸收效率问题。

2.2. 制备方法

纳米颗粒的制备方法主要分为物理法和化学法。物理法如超声波乳化、真空喷雾、超高压均质等技术简单直接,但颗粒的均一性和稳定性控制难度较大。化学法则通过精确控制反应条件,得到更稳定的纳米颗粒。纳米颗粒的大小、形态和表面特性对递送效果有显著影响,因此制备过程的优化成为高效递送系统研发的关键[21] [22]

2.3. 纳米载体选择

针对中药的亲水性和疏水性差异,纳米递送系统的选择需结合药物理化性质、靶向性及生物相容性等因素,以实现高效稳定的药物递送(表2)。

Table 2. Classification, characteristics and hydrophobicity/solubility guidelines for traditional Chinese medicines suitable for nanocarriers

2. 纳米载体分类、特性及亲疏水性中药适配指南

载体类型

典型材料

亲水性中药适配性

疏水性中药适配性

载药率范围

代表应用案例

脂质基载体

磷脂、胆固醇、 甘油三酯

★★☆ (中)

★★★★★ (优)

10%~30%

青蒿素脂质体(磁靶向递送) [34]

聚合物载体

PLGA、壳聚糖、PEG-PLA

★★★★★ (优)

★★★☆☆ (良)

5%~25%

黄芪多糖-PLGA纳米粒(pH响应) [35]

无机载体

金、二氧化硅、 四氧化三铁

★★★☆☆ (良)

★★★★☆ (优)

15%~50%

姜黄–金纳米粒(光热治疗) [36]

杂化载体

脂质-PLGA、 二氧化硅–壳聚糖

★★★★☆ (优)

★★★★☆ (优)

20%~40%

雷公藤甲素液晶脂质 纳米粒[37]

2.3.1. 亲水性中药

亲水性中药成分易溶于水,但其稳定性相对较差,纳米递送系统可采用水溶性材料,如聚合物纳米颗粒或纳米乳液,提高其在体内的稳定性。亲水性纳米载体不仅能有效保护药物,还可在靶向递送过程中实现缓释,提高治疗效果[23],如图1所示。研究表明,基于水溶性材料的纳米颗粒可将亲水性中药稳定封装在内部,延长药物在体内的作用时间[24]。例如,例如,通过无有机溶剂的双重乳液法制备的固体脂质纳米颗粒可长期稳定封装亲水性化合物,确保药物活性成分在体内的有效释放和靶向递送[25]

2.3.2. 疏水性中药

疏水性中药成分因难溶于水而生物利用度较低,纳米递送系统通过脂质体、聚合物纳米颗粒等提高药物的溶解性和稳定性。脂质纳米载体适用于包裹疏水性成分,通过精确调控脂质成分的组成及释放行为,达到靶向递送和控释效果[26]-[28]。然而,脂质载体的生物相容性和稳定性仍有待进一步提高,并需考虑纳米载体与药物间的相互作用,以减少潜在毒性和副作用[29]-[32],如图1所示。例如,脂质体纳米颗粒通过调整载体结构可实现药物的精确控制释放,增强其治疗效果并降低副作用,例如,脂质体纳米颗粒通过调整载体结构可实现药物的精确控制释放,增强其治疗效果并降低副作用[33]

3. 纳米递送系统在中医药领域的应用

纳米递送系统在中医药领域的应用展示了极大的发展潜力,特别是在改善中药活性成分的溶解性、稳定性和生物利用度方面。许多中药活性成分,如萜类、多酚类、黄酮类、生物碱和醌类,具有多样的药理活性,但受限于其水溶性差、体内稳定性低,临床应用效果不佳。纳米技术的发展使纳米载体成为解决这些问题的重要工具,尤其是通过设计多种特异性纳米载体,如牛血清白蛋白纳米颗粒、聚乳酸–羟基乙酸(PLGA)纳米粒和壳聚糖纳米颗粒,可以实现不同活性成分的精准递送,有力推动中药的现代化和国际化[38]。需要进一步强调的是,纳米系统的价值不应仅停留在“提高生物利用度”,其能否在体内形成稳定、可预测的药效窗口,往往取决于载体材料与中药分子之间的分子间相互作用及其对装载与释放行为的共同约束:疏水性成分在脂质体、固体脂质纳米粒或聚合物胶束中的包埋主要由疏水作用与范德华力驱动,多酚、黄酮等芳香环结构还可通过π-π堆积增强载药稳定性并降低突释风险[39] [40];而具有多羟基、羧基或糖链结构的成分更易形成氢键网络或静电吸附,从而改变界面水化层与释放动力学[41]。同时,颗粒进入细胞并非被动过程,其跨膜摄取依赖网格蛋白介导内吞、洞蛋白介导内吞或大胞饮等路径,并受尺寸、形貌与表面电性调控,吞噬细胞对高吸附性颗粒的清除亦会改变组织暴露与疗效表现[42];颗粒弹性等力学属性同样可影响吞噬倾向与摄取命运[43]。进入内体后若无法有效逃逸,药物可能在溶酶体环境中降解而削弱递送效率,因此内体逃逸策略(如质子海绵效应)仍是决定“进入细胞是否等于到达靶点”的关键环节。此外,体内蛋白冠形成会重塑纳米颗粒的生物学身份并影响靶向配体暴露,解释了不少“体外有效、体内失效”的现象[44] [45];PEG化虽可降低调理素吸附并延长循环时间,但也可能降低细胞摄取并引发加速清除等问题,因而更合理的设计趋势是将隐身涂层与可暴露靶向配体及病灶响应脱壳释放相耦合,以实现稳定性与靶向效率的动态平衡[46] [47]

Nano-Particles:纳米颗粒;Active Ingredients of Chinese Medicine:中药活性成分;Endocytosis:内吞作用;Endosome:胞内体;Stimuius-Response:刺激响应;Proton Sponge Effect:质子海绵效应是一种在纳米药物递送系统中,尤其是在某些高分子纳米载体中的独特机制,常被用于提高药物的细胞内释放效率。它主要作用于纳米颗粒进入细胞后,在细胞的内涵体(endosome)或溶酶体(lysosome)中的药物释放过程。

Figure 1. Schematic representation of nanoparticle drug delivery

1. 纳米颗粒药物递送示意图

3.1. 亲水性中药

3.1.1. 丹参提取物(Salvia miltiorrhiza)

丹参提取物含有丹参酮和丹酚酸等水溶性成分,具有抗炎、抗氧化等生物活性,但生物利用度和稳定性较差。通过纳米技术,将丹参酮或丹酚酸包裹在聚合物纳米颗粒或脂质体中,可显著提高其稳定性和靶向性。例如,Ren等人使用牛血清白蛋白(BSA)封装二氢丹参酮(DHT),显著增强了其溶解度和生物相容性。相较于游离DHT,DHT-BSA纳米颗粒在生理盐水中的溶解度明显增加,并表现出对PC12细胞氧化损伤的优越保护作用。此外,DHT-BSA在脑缺血模型中展现了显著疗效,提示其可能的临床应用前景[48]

3.1.2. 黄芪多糖(Astragalus Polysaccharides)

黄芪多糖作为水溶性多糖,具有显著的免疫调节和抗肿瘤活性。然而,稳定性差和靶向性不足限制了其应用。通过将黄芪多糖负载在PLGA纳米颗粒中,可以显著提升其体内稳定性和靶向性。例如,Xu等人设计了pH响应性PLGA纳米颗粒,以包裹OVA和黄芪多糖,结果显示这些纳米颗粒显著增强了免疫反应能力,表现出较高的治疗潜力[35]

3.1.3. 甘草酸(Glycyrrhizic Acid)

甘草酸是具有抗炎、抗过敏等药理作用的甘草活性成分,受限于其低水溶性。通过将甘草酸封装在PLGA纳米颗粒中,显著改善其稳定性和生物利用度,实现长效控制释放。Mahira等人研究的甘草酸-PLGA纳米颗粒在粘膜炎模型中表现出显著的保护作用,表明其潜在的治疗应用[49]

3.1.4. 银杏叶提取物(Ginkgo biloba Extract)

银杏叶提取物中的黄酮类成分具有抗氧化、抗血栓等活性。研究发现,通过纳米技术可以有效提高其溶解度和靶向性。Owczarek等人制备的壳聚糖纳米颗粒在体外表现出对癌细胞的选择性毒性,具有抗癌潜力[50]

3.2. 疏水性中药

3.2.1. 青蒿素(Artemisinin)

青蒿素作为抗疟有效成分,因疏水性限制了其应用。通过磁性纳米颗粒的负载可以显著提高其溶解性和靶向性。Wang等人开发的磁性靶向递送系统利用寄生虫感染的红细胞的顺磁性,实现青蒿素的靶向递送,增强了抗疟效果[34]

3.2.2. 苦参碱(Matrine)

苦参碱作为一种具有抗炎、抗肿瘤活性的中药成分,因其疏水性而限制了其应用。研究人员通过纳米乳剂、纳米脂质体等技术,设计了表面修饰的苦参碱纳米颗粒,显著提高了其溶解性和靶向性。例如,Tan等人的研究开发了甘露糖6-磷酸修饰的苦参碱固体脂质纳米颗粒,用于治疗肝纤维化,结果表明,该纳米颗粒表现出良好的靶向性和缓释效果,有望成为肝纤维化治疗的新策略[51]

3.2.3. 雷公藤甲素(Triptolide)

雷公藤甲素是一种强效的抗炎和免疫抑制剂,然而其强烈的副作用限制了其临床应用。通过纳米技术,可以将雷公藤甲素封装在脂质体或无机纳米颗粒中,实现缓释和靶向递送,减少对正常组织的损伤。例如,李等人研究的载有雷公藤甲素和索拉非尼的纳米颗粒系统展现了良好的肿瘤靶向能力,通过协同作用显著抑制肿瘤细胞的增殖和生长,展示了潜在的临床应用前景[37]

3.2.4. 姜黄素(Curcumin)

姜黄素是一种具有抗炎、抗氧化等多种生物活性的疏水性中药成分,其临床应用因低溶解性受到限制。通过将姜黄素封装在纳米颗粒中,如碳基纳米颗粒或脂质体中,可以显著改善其在体内的溶解性和生物利用度。Danafar等人的研究表明,改良的生物来源碳基纳米颗粒不仅能够实现姜黄素的pH响应释放,还展示出对乳腺癌细胞的显著抗增殖活性[31] [36]

通过这些实例可见,纳米递送系统显著提升了亲水性和疏水性中药的溶解性、稳定性及生物利用度,通过靶向和缓释递送技术,降低了药物副作用,增强了疗效。这些创新性纳米技术的应用不仅为中药现代化提供了可能,还激发了有关其长期安全性和毒性方面的争议,提示未来研究应关注纳米材料在体内的代谢、免疫相容性及长期潜在影响,如表3所示。

Table 3. Nanoparticle delivery systems in the field of traditional Chinese medicine

3. 中医药领域的纳米颗粒递送系统

中药

性质

纳米载体类型

功能改进

丹参提取物

水溶性

抗氧化、抗血栓、抑制血小板聚集及抗凝作用、抗菌消炎、降血脂等

牛血清白蛋白纳米颗粒

提高溶解度和 生物相容性[48]

黄芪多糖

免疫调节、抗肿瘤、调节免疫、 降血糖、抗衰老和抗炎等

聚乳酸–羟基乙酸纳米粒

刺激响应、 增强生物相容性[35]

甘草酸

抗炎、抗溃疡、抗过敏、抗氧化、 免疫调节、抗病毒、抗癌、保肝等

聚乳酸–辅乙醇酸纳米 颗粒

增强稳定性和 生物利用度[49]

银杏叶提取物

抗氧化、抗血栓、改善脑细胞代谢、抗血小板聚集、清除氧自由基生成、改善微循环等

壳聚糖纳米颗粒

药物缓释、靶向递送、 溶解度提升[50]

青蒿素

疏水性

抗疟、抗肿瘤、抑菌杀虫、解热、 抗炎、免疫调节等

磁性纳米颗粒

增强体内分散性、 稳定性和靶向性[34]

苦参碱

抗菌、抗病毒、抗氧化、抗炎、 免疫调节、抗肿瘤等

人血清白蛋白结合 固体脂质纳米颗粒

改善溶解性、靶向性和 生物利用度[51]

雷公藤甲素

抗炎、免疫抑制、抗肿瘤等

液晶脂质纳米颗粒

增加缓释效果、生物 利用度和靶向递送[37]

姜黄素

抗炎、抗癌、抗氧化、抗血管新生、促进伤口愈合、免疫调节、组织修复和神经保护等

生物来源碳基纳米颗粒

刺激响应、受控释放及 良好生物相容性[36]

4. 挑战与展望

4.1. 优点与挑战

纳米颗粒递送系统在提高药物的生物利用度和生物透过性方面展现了显著的优势。通过减小药物颗粒的尺寸,纳米颗粒系统能够增强其穿透生物屏障的能力,如血脑屏障、胃肠屏障等,使药物更容易到达靶部位。这不仅提升了药物的疗效,还显著降低了药物的毒副作用。同时,纳米颗粒技术通常具有生产成本相对较低、易于规模化生产的特点,这为其在临床应用中的推广提供了良好的基础[52]-[54]。然而,尽管纳米颗粒递送系统具备诸多优点,实际应用中仍面临诸多挑战。首先,药物本身的化学性质以及与纳米载体材料的相互作用,可能影响药物在体内的稳定性,这对药物的长效性和可控释放提出了更高的要求。其次,载体材料的潜在毒性仍是一个不可忽视的问题。虽然许多纳米材料被认为具有良好的生物相容性,但其在人体长期滞留和代谢的安全性尚未完全得到确认。最终,这类纳米系统的长期安全性、对免疫系统的影响以及对人体器官的积累效应仍需要经过长期且严格的临床研究和评估[4] [22] [54]-[56]。此外,纳米递送系统在实际应用中的体内外一致性问题仍然困扰研究者。许多纳米药物在体外表现出良好的效果,但在体内的复杂生理环境中,因免疫反应、酶解作用等因素可能导致递送效率和药物活性降低。这些技术瓶颈要求未来的研究在纳米载体设计、表面修饰及药物与纳米材料相互作用机制的理解上取得进一步突破。

与单体递送不同,中药复方的疗效基础常来源于多成分、多靶点的协同网络,而纳米递送若仅将复方简化为单一有效成分的装载,可能会在不经意间削弱“协同”这一核心优势,从而造成临床相关性下降与机制解释偏差[57]。复方纳米递送的关键科学问题不在于能否“共载”,而在于能否实现体内暴露比例的稳定控制,因为多组分在同一载体中的竞争装载、界面吸附与释放耦联,常导致体内比例漂移并破坏协同窗口[58]。因此,面向复方的纳米系统更需要在材料结构上提供“分区装载与分级释放”的工程能力,例如脂质–聚合物杂化颗粒、核壳结构与多层自组装体系被用于将亲水与疏水组分置于不同相域,从而提高共载稳定性并降低突释风险[59]。在组合治疗研究中,精确的载药比例控制已被证明能够显著影响协同疗效强度,提示复方纳米递送的评价应从“是否更强”升级为“是否在体内维持协同所需的比例与时序”。进一步而言,顺序释放或刺激响应释放可使组分在炎症微环境中按预设时间窗释放,从而更接近复方“多环节干预”的系统逻辑,并提高对复杂病程阶段的适配性[60]。因此,复方纳米递送的研究设计建议同时报告多组分药代曲线与比例稳定性,并将共载体系与“简单混合给药(cocktail)”进行对照,以验证纳米化是否真正带来了协同保持与机制增益,而非仅仅提高了某一组分的暴露水平。

4.2. 未来展望

纳米颗粒给药系统在中药中的应用具有巨大的潜力,特别是制备技术的进步使这些系统更加通用。例如,微流体作为一种新兴的制备工具,能够精确控制纳米颗粒的粒径、形态和药物负载比,从而显著提高药物的分散性和递送效率。这一技术进步可以促进持续、大规模的生产,支持中医纳米颗粒给药系统的商业化和临床转化。展望未来,纳米颗粒输送系统的发展可能会整合其他尖端技术,以提高治疗精度和疗效。例如,将CRISPR-Cas9等基因编辑工具与纳米颗粒载体结合起来,可以实现高度靶向的遗传修饰,从而有可能提高某些疾病的治疗特异性和有效性。此外,将纳米颗粒输送与免疫疗法相结合可以增强抗肿瘤免疫反应,产生更强大的治疗效果。然而,由于与免疫相容性和全身毒性相关的潜在问题,关于这些先进技术的最佳整合正在进行辩论,强调需要进行更深入的研究。

从中医角度来看,未来的研究应强调纳米载体与中药活性化合物的相互作用,研究如何有效地将中药分子与纳米材料结合,以提高其稳定性、靶向性和生物利用度。此外,深入研究纳米材料在体内的代谢途径和长期毒性对于全面的安全性评估至关重要,从而确保纳米颗粒为基础的给药系统在临床应用中的可行性。另一个争论的领域涉及传统制剂的复杂性,因为对纳米颗粒系统的适应可能会改变它们的功效或传统的治疗原则,这提出了关于保持中医完整性的问题。

5. 结语

纳米颗粒递送系统为解决中药中疏水性药物溶解性差、生物利用度低等问题提供了有效途径。利用纳米技术,能够将疏水性药物包裹在纳米颗粒中,显著提升其在水中的分散性和稳定性,从而提高药物在体内的吸收与利用率。此外,纳米颗粒递送系统还能够实现中药的靶向递送。通过与特定的靶向分子结合,纳米颗粒可以精准定位病变组织或细胞,增加药物在靶部位的浓度,同时降低对健康组织的毒副作用。一些中药活性成分在储存与运输过程中容易降解或失活,纳米颗粒递送系统则可以通过包裹与保护这些成分,延长其稳定期,进一步提高药物的有效性与安全性,增强中药的药效稳定性。随着纳米技术的持续发展与创新,未来有望开发出更多适用于中医药的纳米递送系统,这将为中医药现代化研究与应用提供全新的思路与方法,推动中医药事业的中国式现代化进程。

基金项目

不同致残进程下类风湿关节炎继发肺间质病变(RA-ILD)中医药疗效评价研究(XM1202306210003)。

NOTES

*通讯作者。

参考文献

[1] Daraee, H., Eatemadi, A., Abbasi, E., Fekri Aval, S., Kouhi, M. and Akbarzadeh, A. (2014) Application of Gold Nanoparticles in Biomedical and Drug Delivery. Artificial Cells, Nanomedicine, and Biotechnology, 44, 410-422. [Google Scholar] [CrossRef] [PubMed]
[2] Selmani, A., Kovačević, D. and Bohinc, K. (2022) Nanoparticles: From Synthesis to Applications and Beyond. Advances in Colloid and Interface Science, 303, Article ID: 102640. [Google Scholar] [CrossRef] [PubMed]
[3] Anwar, M., Muhammad, F. and Akhtar, B. (2021) Biodegradable Nanoparticles as Drug Delivery Devices. Journal of Drug Delivery Science and Technology, 64, Article ID: 102638. [Google Scholar] [CrossRef
[4] Blanco, E., Shen, H. and Ferrari, M. (2015) Principles of Nanoparticle Design for Overcoming Biological Barriers to Drug Delivery. Nature Biotechnology, 33, 941-951. [Google Scholar] [CrossRef] [PubMed]
[5] Goyal, R., Macri, L.K., Kaplan, H.M. and Kohn, J. (2016) Nanoparticles and Nanofibers for Topical Drug Delivery. Journal of Controlled Release, 240, 77-92. [Google Scholar] [CrossRef] [PubMed]
[6] Liu, R., Luo, C., Pang, Z., Zhang, J., Ruan, S., Wu, M., et al. (2023) Advances of Nanoparticles as Drug Delivery Systems for Disease Diagnosis and Treatment. Chinese Chemical Letters, 34, Article ID: 107518. [Google Scholar] [CrossRef
[7] Piao, Y., Bei, H.P., Tam, A., Yang, Y., Zhang, Q., Yang, M., et al. (2019) Calcium Phosphate Nanoparticle-Based Systems for Therapeutic Delivery. In: Theranostic Bionanomaterials, Elsevier, 147-164. [Google Scholar] [CrossRef
[8] Tenchov, R., Bird, R., Curtze, A.E. and Zhou, Q. (2021) Lipid Nanoparticles—From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS Nano, 15, 16982-17015. [Google Scholar] [CrossRef] [PubMed]
[9] Paliwal, R., Paliwal, S.R., Kenwat, R., Kurmi, B.D. and Sahu, M.K. (2020) Solid Lipid Nanoparticles: A Review on Recent Perspectives and Patents. Expert Opinion on Therapeutic Patents, 30, 179-194. [Google Scholar] [CrossRef] [PubMed]
[10] Xu, W., Xing, F.J., Dong, K., You, C., Yan, Y., Zhang, L., et al. (2014) Application of Traditional Chinese Medicine Preparation in Targeting Drug Delivery System. Drug Delivery, 22, 258-265. [Google Scholar] [CrossRef] [PubMed]
[11] Anton, N. and Vandamme, T.F. (2010) Nano-Emulsions and Micro-Emulsions: Clarifications of the Critical Differences. Pharmaceutical Research, 28, 978-985. [Google Scholar] [CrossRef] [PubMed]
[12] Souto, E.B., Cano, A., Martins-Gomes, C., Coutinho, T.E., Zielińska, A. and Silva, A.M. (2022) Microemulsions and Nanoemulsions in Skin Drug Delivery. Bioengineering, 9, Article No. 158. [Google Scholar] [CrossRef] [PubMed]
[13] Moqejwa, T., Marimuthu, T., Kondiah, P.P.D. and Choonara, Y.E. (2022) Development of Stable Nano-Sized Transfersomes as a Rectal Colloid for Enhanced Delivery of Cannabidiol. Pharmaceutics, 14, Article No. 703. [Google Scholar] [CrossRef] [PubMed]
[14] Opatha, S.A.T., Titapiwatanakun, V. and Chutoprapat, R. (2020) Transfersomes: A Promising Nanoencapsulation Technique for Transdermal Drug Delivery. Pharmaceutics, 12, Article No. 855. [Google Scholar] [CrossRef] [PubMed]
[15] Kamaly, N., Yameen, B., Wu, J. and Farokhzad, O.C. (2016) Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chemical Reviews, 116, 2602-2663. [Google Scholar] [CrossRef] [PubMed]
[16] Mthimkhulu, N., Mosiane, K.S., Nweke, E.E., Balogun, M. and Fru, P.N. (2022) Prospects of Delivering Natural Compounds by Polymer-Drug Conjugates in Cancer Therapeutics. Anti-Cancer Agents in Medicinal Chemistry, 22, 1699-1713. [Google Scholar] [CrossRef] [PubMed]
[17] Lin, G., Revia, R.A. and Zhang, M. (2020) Inorganic Nanomaterial‐Mediated Gene Therapy in Combination with Other Antitumor Treatment Modalities. Advanced Functional Materials, 31, Article ID: 2007096. [Google Scholar] [CrossRef] [PubMed]
[18] Shi, Z., Zhou, Y., Fan, T., Lin, Y., Zhang, H. and Mei, L. (2020) Inorganic Nano-Carriers Based Smart Drug Delivery Systems for Tumor Therapy. Smart Materials in Medicine, 1, 32-47. [Google Scholar] [CrossRef
[19] Choi, G., Rejinold, N.S., Piao, H. and Choy, J. (2021) Inorganic-Inorganic Nanohybrids for Drug Delivery, Imaging and Photo-Therapy: Recent Developments and Future Scope. Chemical Science, 12, 5044-5063. [Google Scholar] [CrossRef] [PubMed]
[20] Kumar, A., Sharipov, M., Turaev, A., Azizov, S., Azizov, I., Makhado, E., et al. (2022) Polymer-Based Hybrid Nanoarchitectures for Cancer Therapy Applications. Polymers, 14, Article No. 3027. [Google Scholar] [CrossRef] [PubMed]
[21] Tewabe, A., Abate, A., Tamrie, M., Seyfu, A. and Abdela Siraj, E. (2021) Targeted Drug Delivery—From Magic Bullet to Nanomedicine: Principles, Challenges, and Future Perspectives. Journal of Multidisciplinary Healthcare, 14, 1711-1724. [Google Scholar] [CrossRef] [PubMed]
[22] Najahi-Missaoui, W., Arnold, R.D. and Cummings, B.S. (2020) Safe Nanoparticles: Are We There Yet? International Journal of Molecular Sciences, 22, Article No. 385. [Google Scholar] [CrossRef] [PubMed]
[23] Tarone, A.G., Cazarin, C.B.B. and Marostica Junior, M.R. (2020) Anthocyanins: New Techniques and Challenges in Microencapsulation. Food Research International, 133, Article ID: 109092. [Google Scholar] [CrossRef] [PubMed]
[24] 邓雅思, 谌鑫阳, 龙梦婷, 等. MMPs/pH协同响应的血筒素-普鲁士蓝纳米递药系统联合光热抑制RAFLS细胞增殖和迁移的研究[J]. 中国中药杂志, 2024, 49(11): 2906-2919.
[25] Becker Peres, L., Becker Peres, L., de Araújo, P.H.H. and Sayer, C. (2016) Solid Lipid Nanoparticles for Encapsulation of Hydrophilic Drugs by an Organic Solvent Free Double Emulsion Technique. Colloids and Surfaces B: Biointerfaces, 140, 317-323. [Google Scholar] [CrossRef] [PubMed]
[26] Kong, F., Zhang, J., Li, R., Wang, Z., Wang, W. and Wang, W. (2017) Unique Roles of Gold Nanoparticles in Drug Delivery, Targeting and Imaging Applications. Molecules, 22, Article No. 1445. [Google Scholar] [CrossRef] [PubMed]
[27] Afzal, O., Altamimi, A.S.A., Nadeem, M.S., Alzarea, S.I., Almalki, W.H., Tariq, A., et al. (2022) Nanoparticles in Drug Delivery: From History to Therapeutic Applications. Nanomaterials, 12, Article No. 4494. [Google Scholar] [CrossRef] [PubMed]
[28] Lu, W., Yao, J., Zhu, X. and Qi, Y. (2021) Nanomedicines: Redefining Traditional Medicine. Biomedicine & Pharmacotherapy, 134, Article ID: 111103. [Google Scholar] [CrossRef] [PubMed]
[29] Lin, X., Yang, X., Yang, Y., Zhang, H. and Huang, X. (2023) Research Progress of Traditional Chinese Medicine as Sensitizer in Reversing Chemoresistance of Colorectal Cancer. Frontiers in Oncology, 13, Article ID: 1132141. [Google Scholar] [CrossRef] [PubMed]
[30] Qiao, L., Han, M., Gao, S., Shao, X., Wang, X., Sun, L., et al. (2020) Research Progress on Nanotechnology for Delivery of Active Ingredients from Traditional Chinese Medicines. Journal of Materials Chemistry B, 8, 6333-6351. [Google Scholar] [CrossRef] [PubMed]
[31] Zhang, M., Hu, W., Cai, C., Wu, Y., Li, J. and Dong, S. (2022) Advanced Application of Stimuli-Responsive Drug Delivery System for Inflammatory Arthritis Treatment. Materials Today Bio, 14, Article ID: 100223. [Google Scholar] [CrossRef] [PubMed]
[32] Yañez-Aulestia, A., Gupta, N.K., Hernández, M., Osorio-Toribio, G., Sánchez-González, E., Guzmán-Vargas, A., et al. (2022) Gold Nanoparticles: Current and Upcoming Biomedical Applications in Sensing, Drug, and Gene Delivery. Chemical Communications, 58, 10886-10895. [Google Scholar] [CrossRef] [PubMed]
[33] Zhang, L., Zhu, H., Ye, P., Zhu, L., Ren, Y. and Lei, J. (2024) Controlled Production of Liposomes with Novel Microfluidic Membrane Emulsification for Application of Entrapping Hydrophilic and Lipophilic Drugs. Journal of Industrial and Engineering Chemistry, 131, 470-480. [Google Scholar] [CrossRef
[34] Wang, X., Xie, Y., Jiang, N., Wang, J., Liang, H., Liu, D., et al. (2020) Enhanced Antimalarial Efficacy Obtained by Targeted Delivery of Artemisinin in Heparin-Coated Magnetic Hollow Mesoporous Nanoparticles. ACS Applied Materials & Interfaces, 13, 287-297. [Google Scholar] [CrossRef] [PubMed]
[35] Xu, S., Feng, Z., Zhang, Y., Ni, H., Liu, Z. and Wang, D. (2022) pH-Responsive Astragalus Polysaccharide-Loaded PLGA Nanoparticles as an Adjuvant System to Improve Immune Responses. International Journal of Biological Macromolecules, 222, 1936-1947. [Google Scholar] [CrossRef] [PubMed]
[36] Danafar, H., Salehiabar, M., Barsbay, M., Rahimi, H., Ghaffarlou, M., Arbabi Zaboli, K., et al. (2022) Curcumin Delivery by Modified Biosourced Carbon-Based Nanoparticles. Nanomedicine, 17, 95-105. [Google Scholar] [CrossRef] [PubMed]
[37] Li, Z., Yang, G., Han, L., Wang, R., Gong, C. and Yuan, Y. (2021) Sorafenib and Triptolide Loaded Cancer Cell-Platelet Hybrid Membrane-Camouflaged Liquid Crystalline Lipid Nanoparticles for the Treatment of Hepatocellular Carcinoma. Journal of Nanobiotechnology, 19, Article No. 360. [Google Scholar] [CrossRef] [PubMed]
[38] Qiu, C., Zhang, J.Z., Wu, B., Xu, C.C., Pang, H.H., Tu, Q.C., et al. (2023) Advanced Application of Nanotechnology in Active Constituents of Traditional Chinese Medicines. Journal of Nanobiotechnology, 21, Article No. 456. [Google Scholar] [CrossRef] [PubMed]
[39] Shi, Y., van Steenbergen, M.J., Teunissen, E.A., Novo, L., Gradmann, S., Baldus, M., et al. (2013) Π-Π Stacking Increases the Stability and Loading Capacity of Thermosensitive Polymeric Micelles for Chemotherapeutic Drugs. Biomacromolecules, 14, 1826-1837. [Google Scholar] [CrossRef] [PubMed]
[40] Li, S., Bobbala, S., Vincent, M.P., Modak, M., Liu, Y. and Scott, E.A. (2021) Pi‐Stacking Enhances Stability, Scalability of Formation, Control over Flexibility, and Circulation Time of Polymeric Filamentous Nanocarriers. Advanced NanoBiomed Research, 1, Article ID: 2100063. [Google Scholar] [CrossRef] [PubMed]
[41] Perumal, S., Atchudan, R. and Lee, W. (2022) A Review of Polymeric Micelles and Their Applications. Polymers, 14, Article No. 2510. [Google Scholar] [CrossRef] [PubMed]
[42] Majumder, J. and Minko, T. (2020) Multifunctional and Stimuli-Responsive Nanocarriers for Targeted Therapeutic Delivery. Expert Opinion on Drug Delivery, 18, 205-227. [Google Scholar] [CrossRef] [PubMed]
[43] Rennick, J.J., Johnston, A.P.R. and Parton, R.G. (2021) Key Principles and Methods for Studying the Endocytosis of Biological and Nanoparticle Therapeutics. Nature Nanotechnology, 16, 266-276. [Google Scholar] [CrossRef] [PubMed]
[44] Önal Acet, B., Gül, D., Stauber, R.H., Odabaşı, M. and Acet, Ö. (2024) A Review for Uncovering the “Protein-Nanoparticle Alliance”: Implications of the Protein Corona for Biomedical Applications. Nanomaterials, 14, Article No. 823. [Google Scholar] [CrossRef] [PubMed]
[45] Chou, W. and Lin, Z. (2024) Impact of Protein Coronas on Nanoparticle Interactions with Tissues and Targeted Delivery. Current Opinion in Biotechnology, 85, Article ID: 103046. [Google Scholar] [CrossRef] [PubMed]
[46] Suk, J.S., Xu, Q., Kim, N., Hanes, J. and Ensign, L.M. (2016) Pegylation as a Strategy for Improving Nanoparticle-Based Drug and Gene Delivery. Advanced Drug Delivery Reviews, 99, 28-51. [Google Scholar] [CrossRef] [PubMed]
[47] Zalba, S., ten Hagen, T.L.M., Burgui, C. and Garrido, M.J. (2022) Stealth Nanoparticles in Oncology: Facing the PEG Dilemma. Journal of Controlled Release, 351, 22-36. [Google Scholar] [CrossRef] [PubMed]
[48] Ren, Y., Feng, Y., Xu, K., Yue, S., Yang, T., Nie, K., et al. (2021) Enhanced Bioavailability of Dihydrotanshinone I-Bovine Serum Albumin Nanoparticles for Stroke Therapy. Frontiers in Pharmacology, 12, Article ID: 721988. [Google Scholar] [CrossRef] [PubMed]
[49] Zeeshan, M., Atiq, A., Ain, Q.U., Ali, J., Khan, S. and Ali, H. (2021) Evaluating the Mucoprotective Effects of Glycyrrhizic Acid-Loaded Polymeric Nanoparticles in a Murine Model of 5-Fluorouracil-Induced Intestinal Mucositis via Suppression of Inflammatory Mediators and Oxidative Stress. Inflammopharmacology, 29, 1539-1553. [Google Scholar] [CrossRef] [PubMed]
[50] Owczarek, M., Herczyńska, L., Sitarek, P., Kowalczyk, T., Synowiec, E., Śliwiński, T., et al. (2023) Chitosan Nanoparticles-Preparation, Characterization and Their Combination with Ginkgo Biloba Extract in Preliminary in Vitro Studies. Molecules, 28, Article No. 4950. [Google Scholar] [CrossRef] [PubMed]
[51] Tan, X., Hao, Y., Ma, N., Yang, Y., Jin, W., Meng, Y., et al. (2023) M6p-Modified Solid Lipid Nanoparticles Loaded with Matrine for the Treatment of Fibrotic Liver. Drug Delivery, 30, Article ID: 2219432. [Google Scholar] [CrossRef] [PubMed]
[52] Jogani, V.V., Shah, P.J., Mishra, P., Mishra, A.K. and Misra, A.R. (2008) Intranasal Mucoadhesive Microemulsion of Tacrine to Improve Brain Targeting. Alzheimer Disease & Associated Disorders, 22, 116-124. [Google Scholar] [CrossRef] [PubMed]
[53] Agrawal, M., Saraf, S., Saraf, S., Antimisiaris, S.G., Hamano, N., Li, S., et al. (2018) Recent Advancements in the Field of Nanotechnology for the Delivery of Anti-Alzheimer Drug in the Brain Region. Expert Opinion on Drug Delivery, 15, 589-617. [Google Scholar] [CrossRef] [PubMed]
[54] Udofa, E. and Zhao, Z. (2024) In Situ Cellular Hitchhiking of Nanoparticles for Drug Delivery. Advanced Drug Delivery Reviews, 204, Article ID: 115143. [Google Scholar] [CrossRef] [PubMed]
[55] Bourquin, J., Milosevic, A., Hauser, D., Lehner, R., Blank, F., Petri‐Fink, A., et al. (2018) Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials. Advanced Materials, 30, e1704307. [Google Scholar] [CrossRef] [PubMed]
[56] Shahiwala, A. (2023) Physiological Determinants and Plausible “6R” Roadmap for Clinical Success of Nanomedicines. Nanomedicine, 18, 1207-1222. [Google Scholar] [CrossRef] [PubMed]
[57] Fisusi, F.A. and Akala, E.O. (2019) Drug Combinations in Breast Cancer Therapy. Pharmaceutical Nanotechnology, 7, 3-23. [Google Scholar] [CrossRef] [PubMed]
[58] Aryal, S., Hu, C.J. and Zhang, L. (2011) Polymeric Nanoparticles with Precise Ratiometric Control over Drug Loading for Combination Therapy. Molecular Pharmaceutics, 8, 1401-1407. [Google Scholar] [CrossRef] [PubMed]
[59] Li, B., Shao, H., Gao, L., Li, H., Sheng, H. and Zhu, L. (2022) Nano-Drug Co-Delivery System of Natural Active Ingredients and Chemotherapy Drugs for Cancer Treatment: A Review. Drug Delivery, 29, 2130-2161. [Google Scholar] [CrossRef] [PubMed]
[60] Yusoh, N.A., Ahmad, H., Vallis, K.A. and Gill, M.R. (2025) Advances in Platinum-Based Cancer Therapy: Overcoming Platinum Resistance through Rational Combinatorial Strategies. Medical Oncology, 42, Article No. 262. [Google Scholar] [CrossRef] [PubMed]