中国防痨杂志 ›› 2020, Vol. 42 ›› Issue (4): 398-403.doi: 10.3969/j.issn.1000-6621.2020.04.018
收稿日期:
2019-12-10
出版日期:
2020-04-10
发布日期:
2020-04-07
通信作者:
宋兴华
E-mail:songxinghua19@163.com
基金资助:
XIANG Hai-bin,LIANG Qiu-zhen,LI Xin-xia,SONG Xing-hua()
Received:
2019-12-10
Online:
2020-04-10
Published:
2020-04-07
Contact:
Xing-hua SONG
E-mail:songxinghua19@163.com
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。
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
表1
不同分类递送药物纳米载体的优缺点
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 |
表2
巨噬细胞主动靶向的纳米递药系统的相关报道
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[ |
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[ |
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[ |
2018 | β-葡聚糖 | PLGA | 利福平 | 283.1 | -28.6 | -b | 1.1 | 人THP1巨噬细胞系[ |
2017 | 聚乙二醇 | PLGA | 莫西沙星 | 112.16 | 4.76 | 76.55 | 86.75 | 巨噬细胞[ |
2017 | 甘露糖 | 脂质体 | 利福平 | 720~1380 | 44.4~63.7a | 25.5~44.3 | 6.75~14.53 | 鼠J774巨噬细胞系[ |
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[ |
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[ |
2015 | 霉菌酸 | PLGA | 异烟肼 | 253~929 | 23.3~21.4a | -b | -b | 鼠骨髓巨噬细胞[ |
2015 | 透明质酸 | 生育酚琥珀酸酯胶束 | 利福平 | 238~299 | 23.7~30.9a | -b | 70.01~79.09 | 鼠肺泡MH-S巨噬细胞[ |
2011 | 甘露糖 | 明胶 | 异烟肼 | 343 | 13.17 | 43.2 | -b | 鼠J774巨噬细胞系[ |
2010 | 乳糖 | PLGA | 利福平 | 184 | -3.2 | 42.2 | 78.4±1.14 | 肺泡巨噬细胞[ |
[1] | World Health Organization. Global tuberculosis report 2019. Geneva: World Health Organization, 2019. |
[2] | Kalscheuer R, Palacios A, Anso I , et al. The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochem J, 2019,476(14):1995-2016. |
[3] | Hmama Z, Pena-Diaz S, Joseph S , et al. Immunoevasion and immunosuppression of the macrophage by Mycobacterium tuberculosis. Immunol Rev, 2015,264(1):220-232. |
[4] | Mitchell G, Chen C, Portnoy DA . Strategies Used by Bacteria to Grow in Macrophages. Microbiol Spectr, 2016,4(3). doi: 10.1128/microbiolspec.MCHD-0012-2015. |
[5] | Cardona P, Cardona PJ . Regulatory T Cells in Mycobacterium tuberculosis Infection. Front Immunol, 2019,10:2139. |
[6] | Chai Q, Lu Z, Liu CH . Host defense mechanisms against Mycobacterium tuberculosis (Review). Cell Mol Life Sci, 2019. [Epub ahead of print] |
[7] | de Martino M, Lodi L, Galli L , et al. Immune Response to Mycobacterium tuberculosis: A Narrative Review (Review). Front Pediatr, 2019,7:350. |
[8] | Weiss G, Schaible UE . Macrophage defense mechanisms against intracellular bacteria. Immunol Rev, 2015,264(1):182-203. |
[9] | Singh R, Dwivedi SP, Gaharwar US , et al. Recent updates on drug resistance in Mycobacterium tuberculosis (Review). J Appl Microbiol, 2019. [Epub ahead of print] |
[10] | Lange C, Dheda K, Chesov D , et al. Management of drug-resistant tuberculosis. Lancet, 2019,394(10202):953-966. |
[11] | Delogu G, Goletti D . The spectrum of tuberculosis infection: new perspectives in the era of biologics. J Rheumatol Suppl, 2014,91:11-16. |
[12] | Costa-Gouveia J, Ainsa JA, Brodin P , et al. How can nano-particles contribute to antituberculosis therapy? Drug Discov Today, 2017,22(3):600-607. |
[13] | Cheng H, Chawla A, Yang Y , et al. Development of nanomaterials for bone-targeted drug delivery. Drug Discov Today, 2017,22(9):1336-1350. |
[14] | Sahay G, Alakhova DY, Kabanov AV . Endocytosis of nanomedicines. J Control Release, 2010,145(3):182-195. |
[15] | Patel S, Kim J, Herrera M , et al. Brief update on endocytosis of nanomedicines. Adv Drug Deliv Rev, 2019,144:90-111. |
[16] | Mir M, Ahmed N, Rehman AU . Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf B Bioin-terfaces, 2017,159:217-231. |
[17] | Ding D, Zhu Q . Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics. Mater Sci Eng C Mater Biol Appl, 2018,92:1041-1060. |
[18] | Xu Y, Kim CS, Saylor DM , et al. Polymer degradation and drug delivery in PLGA-based drug-polymer applications: A review of experiments and theories. J Biomed Mater Res B Appl Biomater, 2017,105(6):1692-1716. |
[19] | Pandey R, Zahoor A, Sharma S , et al. Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis. Tuberculosis (Edinb), 2003,83(6):373-378. |
[20] | Sharma A, Sharma S, Khuller GK . Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis. J Antimicrob Chemother, 2004,54(4):761-766. |
[21] | Marcianes P, Negro S, Garcia-Garcia L , et al. Surface-modified gatifloxacin nanoparticles with potential for treating central nervous system tuberculosis. Int J Nanomedicine, 2017,12:1959-1968. |
[22] | Mignani S, Tripathi RP, Chen L , et al. New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers. Pharmaceutics, 2018, 10(3). pii: E105. |
[23] | Bellini RG, Guimaraes AP, Pacheco MA , et al. Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer. J Mol Graph Model, 2015,60:34-42. |
[24] | Dineshkumar P, Panneerselvam T, Brundavani KD , et al. Formulation of Rifampicin Loaded PEGylated 5.0G EDA-PAMAM Dendrimers as Effective Long-Duration Release Drug Carriers. Current Drug Therapy, 2017,12(2):115-126. |
[25] | Klemens SP, Cynamon MH, Swenson CE , et al. Liposome-encapsulated-gentamicin therapy of Mycobacterium avium complex infection in beige mice. Antimicrob Agents Chemother, 1990,34(6):967-970. |
[26] | Merchant Z, Buckton G, Taylor KM , et al. A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections. Curr Pharm Des, 2016,22(17):2577-2598. |
[27] | Pinheiro M, Ribeiro R, Vieira A , et al. Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis. Drug Des Devel Ther, 2016,10:2467-2475. |
[28] | Costa A, Pinheiro M, Magalhaes J , et al. The formulation of nanomedicines for treating tuberculosis. Adv Drug Deliv Rev, 2016,102:102-115. |
[29] | Anderson CF, Grimmett ME, Domalewski CJ , et al. Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020,12(1):e1586. |
[30] | Liang Z, Ni R, Zhou J , et al. Recent advances in controlled pulmonary drug delivery. Drug Discov Today, 2015,20(3):380-389. |
[31] | Mosaiab T, Farr DC, Kiefel MJ , et al. Carbohydrate-based nanocarriers and their application to target macrophages and deliver antimicrobial agents. Adv Drug Deliv Rev, 2019,151/152:94-129. |
[32] | Shivangi, Meena LS . A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected Macrophages Using Biodegradable Nanoparticles. Appl Biochem Biotechnol, 2018,185(3):815-821. |
[33] | Lu E, Franzblau S, Onyuksel H , et al. Preparation of amino-glycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion. J Microencapsul, 2009,26(4):346-354. |
[34] | El Zowalaty ME, Hussein Al Ali SH, Husseiny MI , et al. The ability of streptomycin-loaded chitosan-coated magnetic nanocomposites to possess antimicrobial and antituberculosis activities. Int J Nanomedicine, 2015,10:3269-3274. |
[35] | Maiti D, Tong X, Mou X , et al. Carbon-Based Nanomaterials for Biomedical Applications: A Recent Study. Front Pharmacol, 2018,9:1401. |
[36] | Zou F, Zhou H, Jeong DY , et al. Wrinkled Surface-Mediated Antibacterial Activity of Graphene Oxide Nanosheets. ACS Appl Mater Interfaces, 2017,9(2):1343-1351. |
[37] | De Maio F, Palmieri V, Salustri A , et al. Graphene oxide prevents mycobacteria entry into macrophages through extracellular entrapment. Nanoscale Adv, 2019,1(4):1421-1431. |
[38] | Palmieri V, Papi M, Conti C , et al. The future development of bacteria fighting medical devices: the role of graphene oxide. Expert Rev Med Devices, 2016,13(11):1013-1019. |
[39] | De Maio F, Palmieri V, De Spirito M , et al. Carbon nanomaterials: a new way against tuberculosis. Expert Rev Med Devices, 2019,16(10):863-875. |
[40] | Singh R, Nawale LU, Arkile M , et al. Chemical and biological metal nanoparticles as antimycobacterial agents: A comparative study. Int J Antimicrob Agents, 2015,46(2):183-188. |
[41] | Olakanmi O, Kesavalu B, Pasula R , et al. Gallium nitrate is efficacious in murine models of tuberculosis and inhibits key bacterial Fe-dependent enzymes. Antimicrob Agents Chemother, 2013,57(12):6074-6080. |
[42] | Narayanasamy P, Switzer BL, Britigan BE . Prolonged-acting, multi-targeting gallium nanoparticles potently inhibit growth of both HIV and mycobacteria in co-infected human macrophages. Sci Rep, 2015,5:8824. |
[43] | Choi SR, Britigan BE, Narayanasamy P. Ga(III) Nanoparticles Inhibit Growth of both Mycobacterium tuberculosis and HIV and Release of Interleukin-6 (IL-6) and IL-8 in Coinfected Macrophages. Antimicrob Agents Chemother, 2017, 61(4). pii: e02505-16. |
[44] | Sato MR, Oshiro Junior JA, Machado RT , et al. Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis. Drug Des Devel Ther, 2017,11:909-921. |
[45] | Vieira ACC, Chaves LL, Pinheiro M , et al. Mannosylated solid lipid nanoparticles for the selective delivery of rifampicin to macrophages. Artif Cells Nanomed Biotechnol, 2018, 46 Suppl 1: S 653-663. |
[46] | Maretti E, Costantino L, Rustichelli C , et al. Surface engineering of Solid Lipid Nanoparticle assemblies by methyl alpha-d-mannopyranoside for the active targeting to macrophages in anti-tuberculosis inhalation therapy. Int J Pharm, 2017,528(1/2):440-451. |
[47] | Gao Y, Sarfraz MK, Clas SD , et al. Hyaluronic Acid-Tocopherol Succinate-Based Self-Assembling Micelles for Targeted Delivery of Rifampicin to Alveolar Macrophages. J Biomed Nanotechnol, 2015,11(8):1312-1329. |
[48] | Lemmer Y, Kalombo L, Pietersen RD , et al. Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis. J Control Release, 2015,211:94-104. |
[49] | Mustafa S, Devi VK, Pai RS . Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles. Drug Deliv Transl Res, 2017,7(1):27-36. |
[50] | Bharti S, Kaur G, Jain S , et al. Characteristics and mechanism associated with drug conjugated inorganic nanoparticles. J Drug Target, 2019,27(8):813-829. |
[51] | Pi J, Shen L, Shen H , et al. Mannosylated graphene oxide as macrophage-targeted delivery system for enhanced intracellular M.tuberculosis killing efficiency. Mater Sci Eng C Mater Biol Appl, 2019,103:109777. |
[52] | Costa A, Sarmento B, Seabra V . Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages. Eur J Pharm Sci, 2018,114:103-113. |
[53] | Tukulula M, Gouveia L, Paixao P , et al. Functionalization of PLGA Nanoparticles with 1,3-β-glucan Enhances the Intracellular Pharmacokinetics of Rifampicin in Macrophages. Pharm Res, 2018,35(6):111. |
[54] | Song X, Lin Q, Guo L , et al. Rifampicin loaded mannosylated cationic nanostructured lipid carriers for alveolar macrophage-specific delivery. Pharm Res, 2015,32(5):1741-1751. |
[55] | Saraogi GK, Sharma B, Joshi B , et al. Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis. J Drug Target, 2011,19(3):219-227. |
[56] | Jain SK, Gupta Y, Ramalingam L , et al. Lactose-Conjugated PLGA Nanoparticles for Enhanced Delivery of Rifampicin to the Lung for Effective Treatment of Pulmonary Tuberculosis. PDA J Pharm Sci Technol, 2010,64(3):278-287. |
[57] | Doshi N, Mitragotri S . Macrophages recognize size and shape of their targets. PLoS One, 2010,5(4):e10051. |
[58] | Dua K, Rapalli VK, Shukla SD , et al. Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches. Biomed Pharmacother, 2018,107:1218-1229. |
[1] | 刘晓莉, 雷丽梅, 郭周莉, 黄殷, 徐静, 赵霞, 王燕, 付莉. 结核病患者产生病耻感与领悟社会支持的相关性研究[J]. 中国防痨杂志, 2020, 42(9): 1002-1008. |
[2] | 中国防痨协会学术工作委员会《中国防痨杂志》编辑委员会. 抗结核药品固定剂量复合制剂的临床使用专家共识[J]. 中国防痨杂志, 2020, 42(9): 885-893. |
[3] | 靳鸿建. 我国县级结核病防治服务体系建设及防治工作亟需加强——一位老防痨工作者的意见和建议[J]. 中国防痨杂志, 2020, 42(9): 896-902. |
[4] | 张灿有, 夏辉, 成君. Ⅱ级生物安全柜在结核病实验室中的检测及报告要求[J]. 中国防痨杂志, 2020, 42(9): 903-909. |
[5] | 周林, 刘二勇, 孟庆琳, 陈明亭, 周新华, 高微微, 林明贵, 谢汝明. 《WS 288—2017 肺结核诊断》标准实施后肺结核诊断质量评估分析[J]. 中国防痨杂志, 2020, 42(9): 910-915. |
[6] | 刘二勇, 王前, 周林, 张国钦, 张修磊, 马永成, 杨枢敏, 王毳, 孟庆琳, 陈明亭, 林明贵, 屠德华. 我国部分地区病原学检测阴性肺结核诊断质量现状分析[J]. 中国防痨杂志, 2020, 42(9): 916-920. |
[7] | 孟庆琳, 李进岚, 林定文, 马永成, 侯双翼, 刘年强, 周林. 结核病防治从业人员对新的结核病标准相关知识知晓情况调查分析[J]. 中国防痨杂志, 2020, 42(9): 921-925. |
[8] | 王前, 周林, 刘二勇, 赵雁林, 李涛, 陈明亭, 杨丽佳, 王嘉. 我国县级结核病定点医疗机构结核病诊断能力现况调查研究[J]. 中国防痨杂志, 2020, 42(9): 926-930. |
[9] | 李婷, 何金戈, 苏茜, 李京, 李运葵, 高文凤, 高媛, 杨文. 结核菌素试验在四川省布拖县HIV感染/AIDS患者中筛查结核感染的价值[J]. 中国防痨杂志, 2020, 42(9): 931-936. |
[10] | 李运葵, 何金戈, 苏茜, 李婷, 李京, 高文凤, 杨文, 毛光玉. 结核病症状筛查在四川省布拖县HIV感染/AIDS患者中发现结核病患者的价值[J]. 中国防痨杂志, 2020, 42(9): 937-941. |
[11] | 苏茜, 夏勇, 逯嘉, 王丹霞, 何金戈. 2009—2018年四川省0~14 岁儿童肺结核流行特征分析[J]. 中国防痨杂志, 2020, 42(9): 942-947. |
[12] | 邓亚丽, 张天华, 刘卫平, 张宏伟, 马煜, 李鹏. 2014—2018年陕西省肺结核发病的时空聚集性分析[J]. 中国防痨杂志, 2020, 42(9): 948-955. |
[13] | 董晓, 赵珍, 刘年强, 王森路, 崔燕. 2009—2017年新疆维吾尔自治区老年肺结核发现特征分析[J]. 中国防痨杂志, 2020, 42(9): 956-961. |
[14] | 马廷龙, 韩毅, 程序, 刘志东. 超声抗结核药品电导入联合化疗对胸壁结核的疗效观察[J]. 中国防痨杂志, 2020, 42(9): 968-972. |
[15] | 南海, 张芸, 杨新婷, 段鸿飞. GeneXpert MTB/RIF对骨关节结核诊断价值的Meta分析[J]. 中国防痨杂志, 2020, 42(9): 973-980. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||