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载多西他赛的硬脂酸修饰白及多糖共聚物胶束的体外和体内评价

In vitro and in vivo evaluation of docetaxel-loaded stearic acid-modified Bletilla striata polysaccharide copolymer micelles.

作者信息

Guan Qingxiang, Zhang Guangyuan, Sun Dandan, Wang Yue, Liu Kun, Wang Miao, Sun Cheng, Zhang Zhuo, Li Bingjin, Lv Jiayin

机构信息

School of Pharmacy, Jilin University, Changchun, China.

Faculty of Chemistry, Northeast Normal University, Changchun, China.

出版信息

PLoS One. 2017 Mar 23;12(3):e0173172. doi: 10.1371/journal.pone.0173172. eCollection 2017.

DOI:10.1371/journal.pone.0173172
PMID:28334044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5363891/
Abstract

Bletilla striata polysaccharides (BSPs) have been used in pharmaceutical and biomedical industry, the aim of the present study was to explore a BSPs amphiphilic derivative to overcome its application limit as poorly water-soluble drug carriers due to water-soluble polymers. Stearic acid (SA) was selected as a hydrophobic block to modify B. striata polysaccharides (SA-BSPs). Docetaxel (DTX)-loaded SA-BSPs (DTX-SA-BSPs) copolymer micelles were prepared and characterized. The DTX release percentage in vitro and DTX concentration in vivo was carried out by using high performance liquid chromatography. HepG2 and HeLa cells were subjected to MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazonium bromide) assay to evaluate the cell viability. In vitro evaluation of copolymer micelles showed higher drug encapsulation and loading capacity. The release percentage of DTX from DTX-SA-BSPs copolymer micelles and docetaxel injection was 66.93 ± 1.79% and 97.06 ± 1.56% in 2 days, respectively. The DTX-SA-BSPs copolymer micelles exhibited a sustained release of DTX. A 50% increase in growth inhibition was observed for HepG2 cells treated with DTX-SA-BSPs copolymer micelles as compared to those treated with docetaxel injection for 72 h. DTX-SA-BSPs copolymer micelles presented a similar growth inhibition effect on Hela cells. Furthermore, absolute bioavailability of DTX-SA-BSPs copolymer micelles was shown to be 1.39-fold higher than that of docetaxel injection. Therefore, SA-BSPs copolymer micelles may be used as potential biocompatible polymers for cancer chemotherapy.

摘要

白及多糖（BSPs）已应用于制药和生物医学行业，本研究的目的是探索一种BSPs两亲性衍生物，以克服其作为水溶性聚合物导致的水溶性差的药物载体的应用局限性。选择硬脂酸（SA）作为疏水嵌段来修饰白及多糖（SA-BSPs）。制备并表征了载多西他赛（DTX）的SA-BSPs（DTX-SA-BSPs）共聚物胶束。采用高效液相色谱法测定体外DTX释放率和体内DTX浓度。采用MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）法检测HepG2和HeLa细胞活力，以评估细胞活性。共聚物胶束的体外评价显示出较高的药物包封率和载药量。DTX-SA-BSPs共聚物胶束和多西他赛注射液在2天内的DTX释放率分别为66.93±1.79%和97.06±1.56%。DTX-SA-BSPs共聚物胶束表现出DTX的缓释特性。与多西他赛注射液处理72小时的HepG2细胞相比，用DTX-SA-BSPs共聚物胶束处理的细胞生长抑制率提高了50%。DTX-SA-BSPs共聚物胶束对HeLa细胞呈现出相似的生长抑制作用。此外，DTX-SA-BSPs共聚物胶束的绝对生物利用度比多西他赛注射液高1.39倍。因此，SA-BSPs共聚物胶束可能作为癌症化疗潜在的生物相容性聚合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/fb7037365720/pone.0173172.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/3e9b1f1cbad4/pone.0173172.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/1441c7c216db/pone.0173172.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/88cc0fc5f3f2/pone.0173172.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/cec1a408a0cc/pone.0173172.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/f16852bad6ef/pone.0173172.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/0679008429d3/pone.0173172.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/fb7037365720/pone.0173172.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/3e9b1f1cbad4/pone.0173172.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/1441c7c216db/pone.0173172.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/88cc0fc5f3f2/pone.0173172.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/cec1a408a0cc/pone.0173172.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/f16852bad6ef/pone.0173172.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/0679008429d3/pone.0173172.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561f/5363891/fb7037365720/pone.0173172.g007.jpg

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