- 中国精品科技期刊
- 中国高校百佳科技期刊
- 中国中文核心期刊
- 中国科学引文数据库核心期刊
| Citation: |
LIU Silu, BAI Yun, WANG Jianhua, et al. Preparation of high-drug-loading cantharidin polymer micelle delivery system and its anti-breast cancer activity[J]. J China Pharm Univ, 2024, 55(3): 381 − 389. DOI: 10.11665/j.issn.1000-5048.2023102501
|
The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system (CTD@Sol) of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer. Firstly, CTD@Sol was prepared using sol as the carrier material and CTD as the model drug, and its pharmacological properties such as appearance and morphology, particle size, potential and in vitro release were evaluated. The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer (4T1) cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay; the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry; and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique. The results showed that CTD@Sol appeared as a light pale blue creamy white colour, with an average particle size of (159.73 ± 1.96) nm, a PDI of 0.198 ± 0.006, Zeta potential of –(47.60 ± 1.77) mV, an encapsulation rate of (90.29 ± 1.69)% and a drug loading capacity of (45.00 ± 0. 84)%; the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment (pH 5.5) was significantly faster than that in neutral environment (pH 7.4), suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions. Cellular uptake, cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells, and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug; in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion, this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity (>45%), good pharmacological performance, strong targeting and biosafety, which has the potential to be used in the treatment of breast cancer.
| [1] |
Gao HW, Kang NX, Hu C, et al. Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways[J]. Phytomedicine, 2020, 69: 153197. doi: 10.1016/j.phymed.2020.153197
|
| [2] |
Li KX, Xiao KM, Zhu SJ, et al. Chinese herbal medicine for primary liver cancer therapy: perspectives and challenges[J]. Front Pharmacol, 2022, 13: 889799. doi: 10.3389/fphar.2022.889799
|
| [3] |
XIA Y, JIANG QL, WANG XT, et al. Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells[J]. J China Pharm Univ (中国药科大学学报), 2023, 54(6): 757-768.
|
| [4] |
Yao HL, Zhao JL, Wang Z, et al. Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: an effective strategy for application of a poisonous traditional Chinese medicine[J]. Colloids Surf B Biointerfaces, 2020, 196: 111285. doi: 10.1016/j.colsurfb.2020.111285
|
| [5] |
Zhang ZY. Study on hepatic targeted solid liquid nanoparticles of cantharidin(肝靶向斑蝥素固体脂质纳米粒的研究)[D]. Jinan: Shandong University of Traditional Chinese Medicine, 2010.
|
| [6] |
Miller T, van Colen G, Sander B, et al. Drug loading of polymeric micelles[J]. Pharm Res, 2013, 30(2): 584-595. doi: 10.1007/s11095-012-0903-5
|
| [7] |
Pignatello R, Corsaro R, Bonaccorso A, et al. Soluplus® polymeric nanomicelles improve solubility of BCS-class II drugs[J]. Drug Deliv Transl Res, 2022, 12(8): 1991-2006. doi: 10.1007/s13346-022-01182-x
|
| [8] |
Singh SK, Singh S, Lillard JW Jr, et al. Drug delivery approaches for breast cancer[J]. Int J Nanomedicine, 2017, 12: 6205-6218. doi: 10.2147/IJN.S140325
|
| [9] |
Liu C, Zhong YY, Liu X, et al. Research progress of soluplus carriers in antitumor polymer micelles[J]. Shandong Med J (山东医药), 2021, 61(25): 104-108.
|
| [10] |
Duong VA, Nguyen TTL, Maeng HJ. Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method[J]. Molecules, 2020, 25(20): 4781. doi: 10.3390/molecules25204781
|
| [11] |
Li ZZ, Yue QX, Wang J, et al. Preparation of curcumin-loaded drug micelles and investigation of their in vitro drug release performance[J]. Chin J Exp Tradit Med Form (中国方剂学杂志), 2016, 22(24): 5-8.
|
| [12] |
Smirnov I, Kaszkur Z, Hoell A. Development of nanoparticle bulk morphology analysis: a multidomain XRD approach[J]. Nanoscale, 2023, 15(19): 8633-8642. doi: 10.1039/D3NR00456B
|
| [13] |
Zhu Y, Meng TT, Tan YN, et al. Negative surface shielded polymeric micelles with colloidal stability for intracellular endosomal/lysosomal escape[J]. Mol Pharm, 2018, 15(11): 5374-5386. doi: 10.1021/acs.molpharmaceut.8b00842
|
| [14] |
Yang CL, Wang XC. Lysosome biogenesis: regulation and functions[J]. J Cell Biol, 2021, 220(6): e202102001. doi: 10.1083/jcb.202102001
|
| [15] |
Yang Y. Preparation, characterization, and in vitro and in vivo evaluation of irinotecan poly(lactic-co-glycolic acid)nanoparticles(伊立替康PLGA纳米粒的制备、表征及体内外评价) [D]. Jinan: Shandong University, 2018.
|
| [16] |
Bai Y, Sun YX, Liu SL, et al. Biological effects and in vivo safety study of quercetin nanocarrier drug delivery system on tumor cells[J]. Pharm Biotechnol (药物生物技术), 2022, 29(06): 551-556.
|
| [17] |
Du YF. The mechanism of cantharidin induced apoptosis in breast cancer cells(斑蝥素诱导乳腺癌细胞凋亡机制研究) [D]. Shenyang: China Medical University, 2019.
|
| [18] |
Xu PC, Wang HS, Hu HX, et al. cRGDfK-grafted small-size quercetin micelles for enhancing therapy efficacy of active ingredient from the Chinese medicinal herb[J]. Int J Nanomedicine, 2019, 14: 9173-9184. doi: 10.2147/IJN.S219578
|
| [19] |
Hang HY, Liu CC, Ren DD. Development, application and prospection of flow cytometry[J]. China Biotechnol (中国生物工程杂志), 2019, 39(9): 68-83.
|
| [20] |
Chinen AB, Guan CM, Ferrer JR, et al. Nanoparticle probes for the detection of cancer biomarkers, cells, and tissues by fluorescence[J]. Chem Rev, 2015, 115(19): 10530-10574. doi: 10.1021/acs.chemrev.5b00321
|
| [21] |
Mei D, Lin ZQ, Fu JJ, et al. The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancer[J]. Biomaterials, 2015, 42: 52-65. doi: 10.1016/j.biomaterials.2014.11.044
|
| [22] |
WANG XY, WANG X, QIU LZ, et al. Cytotoxicity and cellular uptake of paclitaxel-loaded carboxymethyl chitosan-rhein polymeric micelles in MCF-7 cells[J]. J China Pharm Univ (中国药科大学学报), 2020, 51(1): 33-37.
|
| [23] |
Li CX, Wang XY, Lu WL, et al. Cellular uptake and in vivo imaging study of emodin conjugate micelles modified with PEG loaded with paclitaxel[J]. Chin J Mod Appl Pharm (中国现代应用药学), 2023, 40(13): 1753-1758.
|
| [1] | REN Weijie, CEN Lifang, ZOU Yi. Research progress of Bruton's tyrosine kinase (BTK) inhibitors in the treatment of inflammatory and immune-mediated diseases[J]. Journal of China Pharmaceutical University, 2024, 55(1): 63-72. DOI: 10.11665/j.issn.1000-5048.2023121103 |
| [2] | YANG Qian, WANG Xiaojian. Research progress of sphingosine kinase 1 inhibitors[J]. Journal of China Pharmaceutical University, 2021, 52(6): 759-768. DOI: 10.11665/j.issn.1000-5048.20210615 |
| [3] | BU Hong, ZHOU Jinpei, ZHANG Huibin. Research progress of mitogen-activated protein kinase interacting kinases inhibitors in tumor immunotherapy[J]. Journal of China Pharmaceutical University, 2021, 52(4): 410-421. DOI: 10.11665/j.issn.1000-5048.20210403 |
| [4] | ZHAO Limeng, WANG Shuzhen. Therapeutic applications of small molecule kinase inhibitors in liver fibrosis[J]. Journal of China Pharmaceutical University, 2018, 49(2): 147-157. DOI: 10.11665/j.issn.1000-5048.20180203 |
| [5] | YUAN Zhong, CHEN Zhuo, LI Qianbin, HU Gaoyun. Advances in research of protein tyrosine phosphatase 1B and its inhibitors[J]. Journal of China Pharmaceutical University, 2018, 49(1): 1-9. DOI: 10.11665/j.issn.1000-5048.20180101 |
| [6] | LI Tonghui, GUO Hao, LU Tao, WANG Yue, LU Shuai, TANG Weifang. Advances in the research of FLT3 inhibitors for acute myeloid leukemia[J]. Journal of China Pharmaceutical University, 2015, 46(2): 153-161. DOI: 10.11665/j.issn.1000-5048.20150203 |
| [7] | ZHANG Yuan, CHENG Yulan, ZHOU Jinpei, ZHANG Huibin. Advances on receptor tyrosine kinase inhibitors taking c-Met as anti-tumor target[J]. Journal of China Pharmaceutical University, 2015, 46(1): 16-27. DOI: 10.11665/j.issn.1000-5048.20150102 |
| [8] | HUANG Fei, ZHU Haijing, ZHOU Xiang, LU Tao, JIAO Yu, TANG Weifang. Progress of Bruton′s tyrosine kinase(BTK)and its inhibitors[J]. Journal of China Pharmaceutical University, 2014, 45(6): 617-624. DOI: 10.11665/j.issn.1000-5048.20140602 |
| [9] | ZHU Yaqi, YAN Fang, DI Bin, YAN Jia, LI Jiachang, LI Yunman. Inhibiting effect of emodin on adriamycin-resistance of K562/ADM cell line[J]. Journal of China Pharmaceutical University, 2014, 45(4): 462-468. DOI: 10.11665/j.issn.1000-5048.20140414 |
| [10] | DONG Gaochao, ZHOU Xiang, TANG Weifang, LU Tao. Advances in the research and development of B-Raf inhibitors[J]. Journal of China Pharmaceutical University, 2014, 45(1): 1-9. DOI: 10.11665/j.issn.1000-5048.20140101 |
Supported by: Beijing Renhe Information Technology Co., Ltd. 
Total visits：292836
DownLoad: