巨噬细胞的抗结核纳米递药系统的应用进展

doi:10.3969/j.issn.1000-6621.2020.04.018

摘要/Abstract

摘要：

结核分枝杆菌作为一种巨噬细胞胞内寄生菌,传统药物治疗存在治疗周期长、生物利用度低、毒性大甚至耐药性增加等局限性问题。抗结核纳米递药系统作为一种抗结核新剂型,可将经济廉价的药物通过主动或被动方式递送到巨噬细胞内,以杀死正在复制或潜伏期的结核分枝杆菌。在此框架下,笔者探讨了抗结核纳米递药系统对巨噬细胞主被动靶向机制,及用于组装纳米递药系统的先进材料。此外,总结了影响靶向递送效率的因素及面临的挑战。

关键词: 结核, 巨噬细胞, 药物载体, 分子靶向治疗, 综述文献(主题), 纳米递药系统

Abstract:

Mycobacterium tuberculosis (MTB) is a facultative intracellular parasite of macrophages, traditional anti-TB therapy have limitations such as long course of treatment, low bio-availability, high systemic toxicity and even may induce drug resistance. As a new method of anti-tuberculous drug administration, the nanoscale drug delivery system can deliver low-cost drugs into macrophages actively or passively to inhibit the replicate or latent MTB. This review explores the active and passive targeting mechanism of anti-tuberculosis nanoscale drug delivery system to macrophages, and advanced materials for assembling nanoscale delivery system. In addition, factors affecting targeted delivery efficiency and challenges are summarized.

Key words: Tuberculosis, Macrophages, Drug carriers, Molecular targeted therapy, Review literature as topic, Nanoscale drug delivery system

向海滨,梁求真,李新霞,宋兴华. 巨噬细胞的抗结核纳米递药系统的应用进展[J]. 中国防痨杂志, 2020, 42(4): 398-403. doi: 10.3969/j.issn.1000-6621.2020.04.018

XIANG Hai-bin,LIANG Qiu-zhen,LI Xin-xia,SONG Xing-hua. Advances in the application of anti-tuberculosis nanoscale drug delivery system targeting macrophages[J]. Chinese Journal of Antituberculosis, 2020, 42(4): 398-403. doi: 10.3969/j.issn.1000-6621.2020.04.018

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分类	纳米载体	优点	缺点
聚合物	明胶、聚乳酸-羟基乙酸共聚物、聚乳酸、聚酸酐、聚丙烯酸酯、树枝状大分子	工艺简单;理化特性可控;生物稳定性高;多途径给药	体内降解速度慢;易蓄积;有机溶剂残留毒性
脂质体	长循环脂质体、糖基脂质体、pH敏感性脂质体	技术成熟;无有机溶剂制备;生物降解性及相容性高	物理稳定性差;半衰期短;药物负载能力低
多糖	藻酸盐、直链淀粉、壳聚糖、透明质酸、环糊精	本质为碳水化合物;毒性极低;廉价;生物相容性高;生物可降解性好	载药量和释放效率低
碳纳米	石墨、氧化石墨烯、碳纳米管、富勒烯和金刚石	载体表面可诱捕细菌且存在大量官能团;易被配体修饰	生物利用度低;生物稳定性差;急性炎症反应和进行性纤维化等毒性
金属载体	银纳米颗粒、镓纳米颗粒、金纳米颗粒、铁纳米颗粒	可干扰MTB代谢;具有抗菌活性	生物利用度低;时间相关的细胞毒性;重金属中毒

文献发表年份	配体	纳米载体	药物	粒径(nm)	电位(mV)	包封率(%)	载药率(%)	靶向细胞
2019	甘露糖	氧化石墨烯	利福平	50~300	-25	-^b	-^b	恒河猴巨噬细胞^[51]
2018	甘露糖	硬脂胺-脂质体	利福平	160~250	25.7	95.5	3.5	人THP1巨噬细胞系^[45]
2018	甘露糖	硬脂胺-脂质体	异烟肼	452~530	26.9~38.6	34.0~50.2	1.6~2.3	人THP1巨噬细胞系^[52]
2018	β-葡聚糖	PLGA	利福平	283.1	-28.6	-^b	1.1	人THP1巨噬细胞系^[53]
2017	聚乙二醇	PLGA	莫西沙星	112.16	4.76	76.55	86.75	巨噬细胞^[49]
2017	甘露糖	脂质体	利福平	720~1380	44.4~63.7^a	25.5~44.3	6.75~14.53	鼠J774巨噬细胞系^[46]
2016	甘露糖	硬脂胺-脂质体	利福布汀	213	37.6	90	-^b	鼠RAW264.7细胞系^[27]
2015	甘露糖	阳离子脂质	利福平	157.4	34.3	91.6	38.4~42.2	鼠肺泡NR8383细胞^[54]
2015	霉菌酸	PLGA	异烟肼	253~929	23.3~21.4^a	-^b	-^b	鼠骨髓巨噬细胞^[48]
2015	透明质酸	生育酚琥珀酸酯胶束	利福平	238~299	23.7~30.9^a	-^b	70.01~79.09	鼠肺泡MH-S巨噬细胞^[47]
2011	甘露糖	明胶	异烟肼	343	13.17	43.2	-^b	鼠J774巨噬细胞系^[55]
2010	乳糖	PLGA	利福平	184	-3.2	42.2	78.4±1.14	肺泡巨噬细胞^[56]