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Article(id=1218290947578843902, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1218290941232861879, articleNumber=1001-2494(2024)15-1408-08, orderNo=null, doi=10.11669/cpj.2024.15.007, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1677945600000, receivedDateStr=2023-03-05, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1768392796654, onlineDateStr=2026-01-14, pubDate=1723046400000, pubDateStr=2024-08-08, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1768392796654, onlineIssueDateStr=2026-01-14, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1768392796654, creator=13701087609, updateTime=1768392796654, updator=13701087609, issue=Issue{id=1218290941232861879, tenantId=1146029695717560320, journalId=1190317699101192196, year='2024', volume='59', issue='15', pageStart='1361', pageEnd='1452', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1768392795141, creator=13701087609, updateTime=1768394622953, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1218298607682376061, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1218290941232861879, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1218298607682376062, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1218290941232861879, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1408, endPage=1415, ext={EN=ArticleExt(id=1218290947880833811, articleId=1218290947578843902, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=In Vitro Release and Anti-Tumor Studies of Paclitaxel-Loaded Rhein Conjugate Micelles, columnId=null, journalTitle=Chinese Pharmaceutical Journal, columnName=null, runingTitle=null, highlight=null, articleAbstract=

OBJECTIVE To study the in vitro release behavior and anti-tumor effect of paclitaxel-loaded rhein conjugate (PTX/TPGS-CR) micelles. METHODS The in vitro drug release behavior of PTX/TPGS-CR micelles in different release media was investigated by dialysis method with Taxol® as the control. The cytotoxicity of PTX/TPGS-CR micelles on mouse breast cancer 4T1 cells was evaluated by MTT assay with Taxol® as a control. The effect of PTX/TPGS-CR micelles on the cell cycle and apoptosis of human cervical carcinoma HeLa cells was detected by flow cytometry. The effect of PTX/TPGS-CR micelles on the migration of HeLa and 4T1 cells was investigated by scratch experiments. RESULTS The results of in vitro release assay showed that 50.84% and 71.38% of PTX in PTX/TPGS-CR micelles were released in pH 7.4 phosphate buffer (PBS) within 12 and 72 h, respectively, 79.19% of PTX in PTX/TPGS-CR micelles were released in pH 5.8 PBS which simulated the tumor microenvironment within 12 h, and almost all of PTX in the micelles was released within 72 h. The results of the cytotoxicity assay showed that PTX/TPGS-CR micelles had a strong inhibitory effect on the proliferation of 4T1 cells and displayed a time-and-concentration-dependent characteristic, with IC50 of 0.321 9 nmol·mL-1 at 72 h. PTX/TPGS-CR micelles could induce early apoptosis and late apoptosis in HeLa and 4T1 cells. PTX/TPGS-CR micelles can induce HeLa cells arrest in G2/M phase (arrested by PTX) and G0/G1 phase, which inhibited cell division and proliferation. PTX/TPGS-CR micelles can inhibit the migration of HeLa and 4T1 cells and reduce tumor metastasis. CONCLUSION PTX/TPGS-CR micelles have good pH-responsive drug release characteristics, which can release drugs slowly in the blood environment and rapidly in the tumor microenvironment. PTX/TPGS-CR micelles could inhibit tumor cells proliferation and migration and promote cell apoptosis. PTX/TPGS-CR micelles have a good tumor treatment potential.

, correspAuthors=Xiaoying WANG, Wei XU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Caixia HUANG, Huizhi OUYANG, Qiuping HUANG, Weili LU, Xiaoying WANG, Wei XU), CN=ArticleExt(id=1218290949629858702, articleId=1218290947578843902, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=载紫杉醇的大黄酸偶联物胶束的体外释放及抗肿瘤研究, columnId=1190352405612040510, journalTitle=中国药学杂志, columnName=论著, runingTitle=null, highlight=null, articleAbstract=

目的 研究载紫杉醇的大黄酸偶联物(PTX/TPGS-CR)胶束的体外释放行为及其体外抗肿瘤效果。方法 采用透析法,以泰素(Taxol®)为对照,考察PTX/TPGS-CR胶束在不同释放介质中的释药行为。采用四甲基偶氮唑蓝(MTT)法,以Taxol®为对照,评估PTX/TPGS-CR胶束对小鼠乳腺癌4T1细胞的细胞毒性。通过流式细胞仪检测PTX/TPGS-CR胶束对人宫颈癌HeLa细胞的细胞周期、凋亡的影响。通过划痕实验考察PTX/TPGS-CR胶束对HeLa、4T1细胞迁移的影响。结果 体外释放实验结果显示,在pH 7.4磷酸盐缓冲液(PBS)中,PTX/TPGS-CR胶束在12 和72 h内分别累积释放50.84%和71.38%;在模拟肿瘤微环境pH 5.8 PBS中,PTX/TPGS-CR胶束在12 h内累积释放79.19%,且72 h几乎完全释放。细胞毒试验结果显示,PTX/TPGS-CR胶束对4T1细胞表现出较强的肿瘤细胞增殖抑制作用,并呈时间和浓度依赖性,72 h时半抑制浓度(IC50)为0.321 9 nmol·mL-1。PTX/TPGS-CR胶束能引起HeLa、4T1细胞发生早期凋亡和晚期凋亡;可使HeLa细胞在PTX阻滞G2/M期的基础上同时增加G0/G1期阻滞,抑制细胞分裂增殖。PTX/TPGS-CR胶束能抑制HeLa、4T1细胞迁移,减少肿瘤转移。结论 PTX/TPGS-CR胶束具有很好的pH响应释药特征,在血液环境中缓释药物,而在肿瘤微环境中实现快速释药;具有很好的肿瘤增殖抑制效果,促进细胞凋亡,抑制肿瘤细胞迁移,具有较好的肿瘤治疗潜力。

, correspAuthors=王晓颖, 徐伟, authorNote=null, correspAuthorsNote=
* 王晓颖,女,博士,教授,硕士生导师 研究方向:缓控释及靶向药物制剂研究 Tel:(0291)22861135;
徐伟,男,博士,教授,博士生导师 研究方向:中药药效物质基础及作用机制研究 Tel:(0591)22861693
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黄彩霞,女,硕士研究生 研究方向:中药制剂与炮制加工

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黄彩霞,女,硕士研究生 研究方向:中药制剂与炮制加工

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黄彩霞,女,硕士研究生 研究方向:中药制剂与炮制加工

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Evaluation and antitumor mechanism of functionalized chitosan-based polymeric micelles for oral delivery of paclitaxel[J]. Int J Pharm, 2022, 625: 122138. DOI:10.1016/j.ijpharm.2022.122138., articleTitle=Evaluation and antitumor mechanism of functionalized chitosan-based polymeric micelles for oral delivery of paclitaxel, refAbstract=null), Reference(id=1218484899707802026, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2020, volume=41, issue=5, pageStart=909, pageEnd=923, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=ZHAO Y, CAO W Q, LIU Y, journalName=高等学校化学学报, refType=null, unstructuredReference=ZHAO Y, CAO W Q, LIU Y. Recent advances in polymeric nano-sized carrier systems[J]. Chem J Chin Univ(高等学校化学学报), 2020, 41(5): 909-923., articleTitle=Recent advances in polymeric nano-sized carrier systems, refAbstract=null), Reference(id=1218484899766522283, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2020, volume=15, issue=14, pageStart=2188, pageEnd=2192, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=WU C Y, CHEN T K, WANG Q, journalName=世界中医药, refType=null, unstructuredReference=WU C Y, CHEN T K, WANG Q. Research progress of puerarin preparation[J]. World Chin Med(世界中医药), 2020, 15(14): 2188-2192., articleTitle=Research progress of puerarin preparation, refAbstract=null), Reference(id=1218484899829436848, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2023, volume=303, issue=null, pageStart=120439, pageEnd=null, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=ZHANG X, XU X Y, WANG X Y, journalName=Carbohydr Polym, refType=null, unstructuredReference=ZHANG X, XU X Y, WANG X Y, et al. Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol[J]. Carbohydr Polym, 2023, 303: 120439. DOI:10.1016/j.carbpol.2022.120439., articleTitle=Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol, refAbstract=null), Reference(id=1218484899888157109, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2020, volume=573, issue=null, pageStart=118840, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=WANG X Y, QIU L Z, WANG X Y, journalName=Int J Pharm, refType=null, unstructuredReference=WANG X Y, QIU L Z, WANG X Y. Evaluation of intestinal permeation enhancement with carboxymethyl chitosan-rhein polymeric micelles for oral delivery of paclitaxel[J]. Int J Pharm, 2020, 573: 118840. DOI:10.1016/j.ijpharm.2019.118840., articleTitle=Evaluation of intestinal permeation enhancement with carboxymethyl chitosan-rhein polymeric micelles for oral delivery of paclitaxel, refAbstract=null), Reference(id=1218484899951071671, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2019, volume=206, issue=null, pageStart=121, pageEnd=131, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=WANG X Y, GUO Y L, QIU L Z, journalName=Carbohydr Polym, refType=null, unstructuredReference=WANG X Y, GUO Y L, QIU L Z, et al. Preparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel[J]. Carbohydr Polym, 2019, 206: 121-131., articleTitle=Preparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel, refAbstract=null), Reference(id=1218484900026569148, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2022, volume=41, issue=2, pageStart=19, pageEnd=27, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=LI M, LIU Y, GONG H, journalName=中国海洋药物杂志, refType=null, unstructuredReference=LI M, LIU Y, GONG H. Preparation and performance study of carboxymethyl chitosan composite hydrogels[J]. Chin J Mar Drugs(中国海洋药物杂志), 2022, 41(2): 19-27., articleTitle=Preparation and performance study of carboxymethyl chitosan composite hydrogels, refAbstract=null), Reference(id=1218484900177564094, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2022, volume=34, issue=5, pageStart=1061, pageEnd=1069, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=PEI D T, ZENG Z W, ZHOU X Y, journalName=化学研究与应用, refType=null, unstructuredReference=PEI D T, ZENG Z W, ZHOU X Y. Preparation and characterization of carboxymethyl chitosan/glucose hydrogel in situ cross-linked by enzyme[J]. Chem Res Appl(化学研究与应用), 2022, 34(5): 1061-1069., articleTitle=Preparation and characterization of carboxymethyl chitosan/glucose hydrogel in situ cross-linked by enzyme, refAbstract=null), Reference(id=1218484900261450174, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2018, volume=49, issue=5, pageStart=596, pageEnd=602, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=WANG X Y, QIU L Z, LI Q Z, journalName=中国药科大学学报, refType=null, unstructuredReference=WANG X Y, QIU L Z, LI Q Z, et al. Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles[J]. J China Pharm Univ(中国药科大学学报), 2018, 49(5): 596-602., articleTitle=Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles, refAbstract=null), Reference(id=1218484900341141954, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2021, volume=43, issue=10, pageStart=2765, pageEnd=2769, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=JIANG L, YANG Y, journalName=中成药, refType=null, unstructuredReference=JIANG L, YANG Y. Research progress on antitumor mechanism of rhubaric acid[J]. Chin Tradit Pat Med(中成药), 2021, 43(10): 2765-2769., articleTitle=Research progress on antitumor mechanism of rhubaric acid, refAbstract=null), Reference(id=1218484900412445125, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2013, volume=49, issue=2, pageStart=175, pageEnd=186, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=GUO Y Y, LUO J, TAN S W, journalName=Eur J Pharm Sci, refType=null, unstructuredReference=GUO Y Y, LUO J, TAN S W, et al. The applications of vitamin E TPGS in drug delivery[J]. Eur J Pharm Sci, 2013, 49(2): 175-186., articleTitle=The applications of vitamin E TPGS in drug delivery, refAbstract=null), Reference(id=1218484900500525513, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2014, volume=11, issue=1, pageStart=59, pageEnd=70, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=GUO Y, CHU M, TAN S, journalName=Mol Pharm, refType=null, unstructuredReference=GUO Y, CHU M, TAN S, et al. Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance[J]. Mol Pharm, 2014, 11(1): 59-70., articleTitle=Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance, refAbstract=null), Reference(id=1218484900609577422, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2019, volume=36, issue=4, pageStart=300, pageEnd=307, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=QIU L Z, WANG X Y, CAO C X, journalName=沈阳药科大学学报, refType=null, unstructuredReference=QIU L Z, WANG X Y, CAO C X, et al. Preparation and characterization of TPGS modified carboxymethyl chitosan-rhein polymeric micelles[J]. J Shenyang Pharm Univ(沈阳药科大学学报), 2019, 36(4): 300-307., articleTitle=Preparation and characterization of TPGS modified carboxymethyl chitosan-rhein polymeric micelles, refAbstract=null), Reference(id=1218484900727017936, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2020, volume=55, issue=7, pageStart=534, pageEnd=541, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=OUYANG H Z, QIU L Z, WANG X Y, journalName=中国药学杂志, refType=null, unstructuredReference=OUYANG H Z, QIU L Z, WANG X Y, et al. Preparation and preliminary evaluation of paclitaxel-loaded TPGS-CR polymeric micelles[J]. Chin Pharm J(中国药学杂志), 2020, 55(7): 534-541., articleTitle=Preparation and preliminary evaluation of paclitaxel-loaded TPGS-CR polymeric micelles, refAbstract=null), Reference(id=1218484900928344531, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2018, volume=22, issue=1, pageStart=589, pageEnd=599, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=SHU L, JIAO W, TING S, journalName=J Cell Mol Med, refType=null, unstructuredReference=SHU L, JIAO W, TING S, et al. The natural agent rhein induces beta-catenin degradation and tumour growth arrest[J]. J Cell Mol Med, 2018, 22(1): 589-599., articleTitle=The natural agent rhein induces beta-catenin degradation and tumour growth arrest, refAbstract=null), Reference(id=1218484900995453399, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2018, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=ZHANG Z R, journalName=Synthesis and characterization of PLGA copolymer and antitumor activity and mechanism of paclitaxel-containing microspheres, refType=null, unstructuredReference=ZHANG Z R. Synthesis and characterization of PLGA copolymer and antitumor activity and mechanism of paclitaxel-containing microspheres[D]. Wuhan: Wuhan University of Technology, 2018., articleTitle=null, refAbstract=null), Reference(id=1218484901054173658, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2018, volume=25, issue=2, pageStart=108, pageEnd=113, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=CHEN Z, LI L B, journalName=药物生物技术, refType=null, unstructuredReference=CHEN Z, LI L B. Preparation and in vitro Evaluation of Novel Paclitaxel-Loaded Liposomes[J]. Pharm Biotechnol(药物生物技术), 2018, 25(2): 108-113., articleTitle=Preparation and in vitro Evaluation of Novel Paclitaxel-Loaded Liposomes, refAbstract=null), Reference(id=1218484901129671133, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=XU C, journalName=Construction of co-loaded paclitaxel and siRNA-E7 nanodelivery system encapsulated by HeLa cell membrane and its therapeutic effect on cervical cancer, refType=null, unstructuredReference=XU C. Construction of co-loaded paclitaxel and siRNA-E7 nanodelivery system encapsulated by HeLa cell membrane and its therapeutic effect on cervical cancer[D]. Shanghai: Shanghai Jiao Tong University, 2020., articleTitle=null, refAbstract=null), Reference(id=1218484901205168608, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2022, volume=1190, issue=null, pageStart=339248, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=YIN Y G, KONG X Q, LI M, journalName=Anal Chim Acta, refType=null, unstructuredReference=YIN Y G, KONG X Q, LI M, et al. Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples[J]. Anal Chim Acta, 2022, 1190: 339248. DOI:10.1016/j.aca.2021.339248., articleTitle=Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples, refAbstract=null), Reference(id=1218484901289054691, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2021, volume=16, issue=15, pageStart=137, pageEnd=139, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=ZHAO Y, journalName=中国实用医药, refType=null, unstructuredReference=ZHAO Y. Clinical adverse drug reactions of paclitaxel for injection (albumin binding type)[J]. Chin Pract Med(中国实用医药), 2021, 16(15): 137-139., articleTitle=Clinical adverse drug reactions of paclitaxel for injection (albumin binding type), refAbstract=null), Reference(id=1218484901419078117, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, doi=null, pmid=null, pmcid=null, year=2021, volume=32, issue=3, pageStart=328, pageEnd=333, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=WANG Y W, MENG L, LIU X, journalName=中国药房, refType=null, unstructuredReference=WANG Y W, MENG L, LIU X. ADR signal mining of paclitaxel for injection(albumin-bound type) based on FDA adverse event database[J]. 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caption=PTX/TPGS-CR PMs对HeLa细胞周期影响的流式细胞图, figureFileSmall=wGlmgf7mEzrP1+HfWM//Jw==, figureFileBig=QiKc3DGl/XhFJW9U5Eiapg==, tableContent=null), ArticleFig(id=1218484898386596209, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=EN, label=Fig.5, caption=Effects of PTX/TPGS-CR PMs on the migration of HeLa cells(×100), figureFileSmall=ZKD9g0tDo/Hu05AmtQNXPQ==, figureFileBig=Cd/pxUmJ05amY5BREaj5pQ==, tableContent=null), ArticleFig(id=1218484898483065208, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=CN, label=图5, caption=PTX/TPGS-CR PMs对HeLa细胞迁移作用影响(×100), figureFileSmall=ZKD9g0tDo/Hu05AmtQNXPQ==, figureFileBig=Cd/pxUmJ05amY5BREaj5pQ==, tableContent=null), ArticleFig(id=1218484898550174075, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=EN, label=Fig.6, caption=Effects of PTX/TPGS-CR PMs on the migration of 4T1 cells(×100), figureFileSmall=d2H38kBJgTrkfQHp5KG5Nw==, figureFileBig=RR9Eza3MbhESSCXgnppDPw==, tableContent=null), ArticleFig(id=1218484898613088639, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=CN, label=图6, caption=不同浓度的PTX/TPGS-CR PMs对4T1细胞迁移作用的影响(×100), figureFileSmall=d2H38kBJgTrkfQHp5KG5Nw==, figureFileBig=RR9Eza3MbhESSCXgnppDPw==, tableContent=null), ArticleFig(id=1218484898688586115, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=EN, label=Tab.1, caption=

In vitro release curve fitting equation of PTX/TPGS-CR PMs

, figureFileSmall=null, figureFileBig=null, tableContent=
Model Taxol® in pH 7.4 PTX/TPGS-CR PMs in pH 7.4 PTX/TPGS-CR PMs in pH 5.8 PTX/TPGS-CR PMs in pH 4.5
Equation r2 Equation r2 Equation r2 Equation r2
Zero-order kinetics Qt=1.208t+30.641 0.786 Qt=0.791t+27.122 0.777 Qt=1.053t+36.920 0.695 Qt=1.256t+14.34 0.989
First-order kinetics Qt=94.256(1-e-0.108t) 0.960 Qt=67.885(1-e-0.133t) 0.858 Qt=89.893(1-e-0.164t) 0.946 Qt=117.74(1-e-0.023t) 0.918
Higuchi Qt=11.690t1/2+12.526 0.938 Qt=7.654t1/2+15.275 0.927 Qt=10.431t1/2+20.234 0.876 Qt=11.04t1/2-0.336 0.954
Weibull Qt=101.76(1- e - 0.076 ( t + 0.49 ) ) 0.744) 0.991 Qt=73.46(1- e - 0.078 ( t + 1.7 ) ) 0.077) 0.972 Qt=93.9(1- e - 0.125 ( t + 0.47 ) ) 0.76) 0.980 Qt=178.95(1- e - 0.010   3 ( t + 11.55 ) ) 1.12) 0.990
), ArticleFig(id=1218484898801832325, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=CN, label=表1, caption=

PTX/TPGS-CR PMs体外释放曲线拟合方程

, figureFileSmall=null, figureFileBig=null, tableContent=
Model Taxol® in pH 7.4 PTX/TPGS-CR PMs in pH 7.4 PTX/TPGS-CR PMs in pH 5.8 PTX/TPGS-CR PMs in pH 4.5
Equation r2 Equation r2 Equation r2 Equation r2
Zero-order kinetics Qt=1.208t+30.641 0.786 Qt=0.791t+27.122 0.777 Qt=1.053t+36.920 0.695 Qt=1.256t+14.34 0.989
First-order kinetics Qt=94.256(1-e-0.108t) 0.960 Qt=67.885(1-e-0.133t) 0.858 Qt=89.893(1-e-0.164t) 0.946 Qt=117.74(1-e-0.023t) 0.918
Higuchi Qt=11.690t1/2+12.526 0.938 Qt=7.654t1/2+15.275 0.927 Qt=10.431t1/2+20.234 0.876 Qt=11.04t1/2-0.336 0.954
Weibull Qt=101.76(1- e - 0.076 ( t + 0.49 ) ) 0.744) 0.991 Qt=73.46(1- e - 0.078 ( t + 1.7 ) ) 0.077) 0.972 Qt=93.9(1- e - 0.125 ( t + 0.47 ) ) 0.76) 0.980 Qt=178.95(1- e - 0.010   3 ( t + 11.55 ) ) 1.12) 0.990
), ArticleFig(id=1218484898873135497, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=EN, label=Tab.2, caption=

Effects of PTX/TPGS-CR PMs on apoptosis rate of HeLa and 4T1 cells.n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Cells Groups t/h Early apoptosis/% Late apoptosis/% Total apoptosis/%
HeLa Control 3.28±1.31 5.38±1.12 8.66±0.47
PTX/TPGS-CR PMs 24 18.46±1.212) 14.07±1.091) 32.53±1.922)
PTX/TPGS-CR PMs 48 29.19±0.862) 51.58±1.162) 80.77±0.632)
4T1 Control 1.01±0.08 5.08±0.71 6.08±0.79
PTX/TPGS-CR PMs 24 3.32±1.19 8.44±2.1 11.76±3.28
PTX/TPGS-CR PMs 48 7.04±2.071) 15.07±1.951) 22.11±4.021)
), ArticleFig(id=1218484898957021579, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=CN, label=表2, caption=

PTX/TPGS-CR PMs对HeLa、4T1细胞凋亡率的影响。n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Cells Groups t/h Early apoptosis/% Late apoptosis/% Total apoptosis/%
HeLa Control 3.28±1.31 5.38±1.12 8.66±0.47
PTX/TPGS-CR PMs 24 18.46±1.212) 14.07±1.091) 32.53±1.922)
PTX/TPGS-CR PMs 48 29.19±0.862) 51.58±1.162) 80.77±0.632)
4T1 Control 1.01±0.08 5.08±0.71 6.08±0.79
PTX/TPGS-CR PMs 24 3.32±1.19 8.44±2.1 11.76±3.28
PTX/TPGS-CR PMs 48 7.04±2.071) 15.07±1.951) 22.11±4.021)
), ArticleFig(id=1218484899028324748, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=EN, label=Tab.3, caption=

Effects of PTX/TPGS-CR PMs on HeLa cell cycle.n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Groups t/h G0/G1
phase/%		 S phase
/%		 G2/M phase
/%
Control - 57.99±0.83 15.65±0.61 26.36±0.27
Taxol® 24 13.83±2.49 22.68±0.97 63.49±3.45
Taxol® 48 0.35±0.35 25.55±0.52 74.04±0.48
PTX/TPGS-CR PMs 24 15.07±2.52 18.84±4.88 66.08±5.24
PTX/TPGS-CR PMs 48 2.69±1.49 25.35±0.52 71.95±1.02
), ArticleFig(id=1218484899141570962, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1218290947578843902, language=CN, label=表3, caption=

PTX/TPGS-CR PMs对HeLa细胞周期的影响。n=3,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=
Groups t/h G0/G1
phase/%		 S phase
/%		 G2/M phase
/%
Control - 57.99±0.83 15.65±0.61 26.36±0.27
Taxol® 24 13.83±2.49 22.68±0.97 63.49±3.45
Taxol® 48 0.35±0.35 25.55±0.52 74.04±0.48
PTX/TPGS-CR PMs 24 15.07±2.52 18.84±4.88 66.08±5.24
PTX/TPGS-CR PMs 48 2.69±1.49 25.35±0.52 71.95±1.02
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载紫杉醇的大黄酸偶联物胶束的体外释放及抗肿瘤研究
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黄彩霞 , 欧阳惠枝 , 黄秋萍 , 陆伟利 , 王晓颖 * , 徐伟 *
中国药学杂志 | 论著 2024,59(15): 1408-1415
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中国药学杂志 | 论著 2024, 59(15): 1408-1415
载紫杉醇的大黄酸偶联物胶束的体外释放及抗肿瘤研究
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黄彩霞, 欧阳惠枝, 黄秋萍, 陆伟利, 王晓颖*, 徐伟*
作者信息
  • 福建中医药大学药学院, 福州 350122

    • 黄彩霞,女,硕士研究生 研究方向:中药制剂与炮制加工

通讯作者:

* 王晓颖,女,博士,教授,硕士生导师 研究方向:缓控释及靶向药物制剂研究 Tel:(0291)22861135;
徐伟,男,博士,教授,博士生导师 研究方向:中药药效物质基础及作用机制研究 Tel:(0591)22861693
In Vitro Release and Anti-Tumor Studies of Paclitaxel-Loaded Rhein Conjugate Micelles
Caixia HUANG, Huizhi OUYANG, Qiuping HUANG, Weili LU, Xiaoying WANG*, Wei XU*
Affiliations
  • College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
出版时间: 2024-08-08 doi: 10.11669/cpj.2024.15.007
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摘要
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目的 研究载紫杉醇的大黄酸偶联物(PTX/TPGS-CR)胶束的体外释放行为及其体外抗肿瘤效果。方法 采用透析法,以泰素(Taxol®)为对照,考察PTX/TPGS-CR胶束在不同释放介质中的释药行为。采用四甲基偶氮唑蓝(MTT)法,以Taxol®为对照,评估PTX/TPGS-CR胶束对小鼠乳腺癌4T1细胞的细胞毒性。通过流式细胞仪检测PTX/TPGS-CR胶束对人宫颈癌HeLa细胞的细胞周期、凋亡的影响。通过划痕实验考察PTX/TPGS-CR胶束对HeLa、4T1细胞迁移的影响。结果 体外释放实验结果显示,在pH 7.4磷酸盐缓冲液(PBS)中,PTX/TPGS-CR胶束在12 和72 h内分别累积释放50.84%和71.38%;在模拟肿瘤微环境pH 5.8 PBS中,PTX/TPGS-CR胶束在12 h内累积释放79.19%,且72 h几乎完全释放。细胞毒试验结果显示,PTX/TPGS-CR胶束对4T1细胞表现出较强的肿瘤细胞增殖抑制作用,并呈时间和浓度依赖性,72 h时半抑制浓度(IC50)为0.321 9 nmol·mL-1。PTX/TPGS-CR胶束能引起HeLa、4T1细胞发生早期凋亡和晚期凋亡;可使HeLa细胞在PTX阻滞G2/M期的基础上同时增加G0/G1期阻滞,抑制细胞分裂增殖。PTX/TPGS-CR胶束能抑制HeLa、4T1细胞迁移,减少肿瘤转移。结论 PTX/TPGS-CR胶束具有很好的pH响应释药特征,在血液环境中缓释药物,而在肿瘤微环境中实现快速释药;具有很好的肿瘤增殖抑制效果,促进细胞凋亡,抑制肿瘤细胞迁移,具有较好的肿瘤治疗潜力。

紫杉醇  /  聚合物胶束  /  体外释放  /  抗肿瘤  /  细胞实验

OBJECTIVE To study the in vitro release behavior and anti-tumor effect of paclitaxel-loaded rhein conjugate (PTX/TPGS-CR) micelles. METHODS The in vitro drug release behavior of PTX/TPGS-CR micelles in different release media was investigated by dialysis method with Taxol® as the control. The cytotoxicity of PTX/TPGS-CR micelles on mouse breast cancer 4T1 cells was evaluated by MTT assay with Taxol® as a control. The effect of PTX/TPGS-CR micelles on the cell cycle and apoptosis of human cervical carcinoma HeLa cells was detected by flow cytometry. The effect of PTX/TPGS-CR micelles on the migration of HeLa and 4T1 cells was investigated by scratch experiments. RESULTS The results of in vitro release assay showed that 50.84% and 71.38% of PTX in PTX/TPGS-CR micelles were released in pH 7.4 phosphate buffer (PBS) within 12 and 72 h, respectively, 79.19% of PTX in PTX/TPGS-CR micelles were released in pH 5.8 PBS which simulated the tumor microenvironment within 12 h, and almost all of PTX in the micelles was released within 72 h. The results of the cytotoxicity assay showed that PTX/TPGS-CR micelles had a strong inhibitory effect on the proliferation of 4T1 cells and displayed a time-and-concentration-dependent characteristic, with IC50 of 0.321 9 nmol·mL-1 at 72 h. PTX/TPGS-CR micelles could induce early apoptosis and late apoptosis in HeLa and 4T1 cells. PTX/TPGS-CR micelles can induce HeLa cells arrest in G2/M phase (arrested by PTX) and G0/G1 phase, which inhibited cell division and proliferation. PTX/TPGS-CR micelles can inhibit the migration of HeLa and 4T1 cells and reduce tumor metastasis. CONCLUSION PTX/TPGS-CR micelles have good pH-responsive drug release characteristics, which can release drugs slowly in the blood environment and rapidly in the tumor microenvironment. PTX/TPGS-CR micelles could inhibit tumor cells proliferation and migration and promote cell apoptosis. PTX/TPGS-CR micelles have a good tumor treatment potential.

paclitaxel  /  polymeric micelle  /  in vitro release  /  anti-tumor  /  cell experiment
黄彩霞, 欧阳惠枝, 黄秋萍, 陆伟利, 王晓颖, 徐伟. 载紫杉醇的大黄酸偶联物胶束的体外释放及抗肿瘤研究. 中国药学杂志, 2024 , 59 (15) : 1408 -1415 . DOI: 10.11669/cpj.2024.15.007
Caixia HUANG, Huizhi OUYANG, Qiuping HUANG, Weili LU, Xiaoying WANG, Wei XU. In Vitro Release and Anti-Tumor Studies of Paclitaxel-Loaded Rhein Conjugate Micelles[J]. Chinese Pharmaceutical Journal, 2024 , 59 (15) : 1408 -1415 . DOI: 10.11669/cpj.2024.15.007
正文
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聚合物胶束(polymeric micelles,PMs)是一类由两亲性聚合物在水性溶剂中自发形成的具有壳-核结构的聚集体[1-3]。其具有良好的自组装能力、增溶疏水性药物的能力;可根据药物应用需要选择适宜的胶束载体材料;可通过在胶束的亲水链段连接特异性抗体、配体或某些刺激敏感系统等,实现药物定位传递[4-6]。
羧甲基壳聚糖(carboxymethyl chitosan,CMCS)为壳聚糖水溶性衍生物,具有良好的生物相容性、抗菌活性及生物降解性等[7-8]。CMCS上具有多种官能团,例如-NH2、-OH和-COOH,具有良好的可修饰性[9]。大黄酸(rhein,R)是一种广泛存在于中草药中的蒽醌类化合物,具有多种药理活性。近年来发现该成分可通过调控多种分子、信号途径来发挥抗肿瘤作用[10],且与抗肿瘤药物紫杉醇(paclitaxel,PTX)在体外实验中表现出协同抗肿瘤作用[6]。目前,作为P-糖蛋白抑制剂的D-α-生物酚聚乙二醇1 000琥珀酸酯(D-α-tocopheryl polyethylene glycol 1 000 succinate,TPGS)能减少由能量依赖性外排泵引起的药物流出[11-12],已经被广泛应用于逆转癌症多药耐药(multidrug resistance,MDR)的研究。
本课题组前期通过丁二酸酐(SA)开环反应,合成TPGS-SA中间体,然后通过酰化反应,将TPGS-SA与疏水性R接枝于亲水骨架CMCS 上,制备了两亲性TPGS修饰的羧甲基壳聚糖-大黄酸偶联物(TPGS-CR)并确定了其结构[13]。该偶联物能在水中自组装成胶束并能包载PTX,课题组优化了载PTX的TPGS-CR偶联物胶束(PTX/TPGS-CR PMs)制备工艺,并对其安全性进行了初步研究[14]。本实验将进一步研究PTX/TPGS-CR PMs在不同释放介质中的释药行为,考察PTX/TPGS-CR PMs的细胞毒性及其对细胞周期、细胞凋亡及迁移的影响,为其体内抗肿瘤研究提供依据。
1 材料
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1.1 试剂
TPGS-CR偶联物(自制);PTX/TPGS-CR胶束[自制,PTX载药量为(44.17±0.64)%];紫杉醇(PTX,上海金和药业有限公司,批号:201801004,纯度>98%);多西紫杉醇(DTX,上海阿拉丁生化科技股份有限公司,批号:20180322,纯度>98%);泰素®(Taxol®,百时美施贵宝,批号:7J04591);四甲基偶氮唑蓝(MTT,德国Bio Froxx公司,1334MG250);96孔细胞培养板、流式细胞管(12 mm×75 mm,5 mL)(康宁公司);细胞周期检测试剂盒(凯基生物科技有限公司,KGA512);细胞凋亡检测试剂盒(大连美伦生物技术有限公司,MA0334);二甲亚砜(DMSO,国药集团试剂有限公司,分析级);聚氧乙烯蓖麻油(阿拉丁试剂有限公司,C1812053);乙腈为色谱纯,其他试剂均为分析纯。
1.2 仪器
高效液相色谱仪(LC20-AT型,日本岛津公司);电热恒温振荡水槽(DKZ型,上海一恒科技公司);细胞培养箱(Thermo 311型,美国Thermo公司);多功能酶标仪(Infinite M200Pro型,瑞士TECAN公司);十万分之一电子天平(MS105DU型,瑞士METTLER TOLEDO集团);流式细胞仪(FACSCantoTM Ⅱ型,美国碧迪公司);倒置显微镜(CKX31型,日本OLYMPUS公司)。
1.3 细胞株
人宫颈癌(HeLa)细胞、小鼠乳腺癌(4T1)细胞购自中国科学院上海细胞库。
2 方法
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2.1 PTX含量测定方法的建立
2.1.1 HPLC法色谱条件
色谱柱:Platisil ODS(4.6 mm×250 mm,5 μm);流动相:乙腈-水(55:45),流速:1.0 mL·min-1;柱温:30 ℃;检测波长:227 nm;进样量:20 μL。
2.1.2 标准曲线的制备
精密称定PTX 3.0 mg,置10 mL的量瓶中,加乙腈稀释至刻度线,得300 μg·mL-1的储备液。以乙腈为溶剂,逐步稀释该储备液得质量浓度分别为25、20、15、10、7.5、5、2.5、1 μg·mL-1的PTX溶液。于10 mL离心管中加各浓度的PTX溶液200 μL和内标DTX(50 μg·mL-1)的乙腈溶液100 μL,挥干溶剂后,加入5 mL的空白释放介质。所有样品分别用二氯甲烷3 mL进行萃取,涡旋5 min,收集2.5 mL二氯甲烷萃取液至5 mL离心管中,真空抽干溶剂,用200 μL乙腈涡旋5 min复溶,14 000 r·min-1离心10 min,取上清液按“2.1.1”项下色谱条件测定,记录PTX和DTX的峰面积。以APTX与ADTX的峰面积比值(Y)对PTX质量浓度(ρ)作图,得回归方程,每分析批建立1条标准曲线。
2.1.3 精密度
配制PTX低、中、高(2、5、10 μg·mL-1)质量浓度的样品按“2.1.2”项下方法处理分析样品,当天连续测定5次,连续测定3 d,计算日内、日间精密度。
2.1.4 提取回收率
使用PTX低、中、高(2、5、10 μg·mL-1)质量浓度的样品测得峰面积A1。取空白介质同“2.1.2”项下方法处理分析样品,在萃取所得的上清液中加入低、中、高质量浓度的PTX标准液,之后操作同前,测得峰面积A2。A1/A2即为提取回收率。
2.2 体外释放实验
采用透析法,以pH 7.4、5.8、4.5的磷酸盐缓冲液(PBS)加水杨酸钠(浓度为0.8 mol·L-1)作为释放介质,评估PTX/TPGS-CR PMs在不同释放介质中的释放PTX的情况。
取PTX/TPGS-CR PMs冻干品,精密称定,加入0.9%氯化钠注射液探头超声溶解稀释,加释放介质稀释至含PTX质量浓度为250 μg·mL-1,立即取1 mL于透析袋[截留相对分子质量(MWCO)=14 000]内,密封后浸没于盛有100 mL释放介质的烧杯内,在100 r·min-1和37 ℃下进行PTX/TPGS-CR PMs在不同pH 释放介质中的体外释放实验。按设定时间间隔(0.25、0.5、1、2、4、6、8、12、24、36、48、60和72 h),取释放液5 mL置于10 mL离心管(其内有已挥干乙腈溶剂的内标DTX 5 μg)中,同时补充等体积的空白释放介质,样品用二氯甲烷3 mL进行萃取(pH为5.8和4.5的释放液萃取前调pH为中性),涡旋5 min,收集二氯甲烷萃取液2.5 mL于5 mL离心管中,真空抽干溶剂,用200 μL乙腈涡旋5 min复溶,14 000 r·min-1离心10 min,取上清液,按“2.1.1”项下HPLC法色谱条件测定释放液中的PTX量,计算累积释放量,绘制释放曲线。实验以PTX市售制剂Taxol®注射液为对照。每种介质中的释放平行操作3份,并使透析袋透过面积大小相等。累积释放百分率(Qt)的计算见公式1。
Qt(%)=(ρn×V+ ∑ n = 1 n - 1 ρ×V0)/M×100%
公式中,ρn为第n次取样时释放液中PTX的质量浓度,V为总释放介质体积,V0为取样体积,M为用于释放的PTX总量。
2.3 细胞培养及传代
当培养瓶中细胞贴壁达80%~90%后可进行传代培养。将质量分数0.25%胰蛋白酶预热。弃旧培养基,加入1~2 mL PBS,洗涤后弃去,洗涤2次。加1 mL胰酶,培养箱中孵育消化,细胞变圆且间隙增大、轻拍瓶壁见细胞脱落时即可停止,加入2 mL完全培养基终止消化。轻吹打瓶壁上的细胞,使脱落成细胞悬浮液,1 000 r·min-1离心4 min,弃上清液,加适量完全培养液重悬,1:3~1:4比例传代,继续培养。
2.4 细胞毒性实验
取处于对数生长的4T1细胞,消化并调整浓度至5×105·mL-1,向96孔板中加入100 μL细胞悬浮液,孵育24 h,小心吸去培养液。加入用完全培养液稀释配制的浓度梯度实验药液,每孔150 μL,每个浓度平行6个孔,含细胞不给药物即正常组,设置空白对照组。试验药液包括Taxol®注射剂的混合溶剂(蓖麻油聚氧乙烯醚-无水乙醇=1:1)组、TPGS-CR偶联物组、Taxol®组和PTX/TPGS-CR PMs组。混合溶剂和TPGS-CR偶联物浓度按其在相应浓度的Taxol®和PTX/TPGS-CR PMs中的量计算。加药后24、48和72 h取出,吸除上清液,每孔加入100 μL PBS稀释的MTT溶液(0.5 mg·mL-1),孵育4 h,轻轻吸弃上清。每孔用150 μL的DMSO溶解甲瓒结晶。酶标仪测定吸光度值(570 nm)。细胞的存活率按公式2计算:
细胞存活率(%)=(A实验组-A空白)/(A正常组-A空白)×100%
公式中,A实验组是实验组的吸光度,A正常组是空白培养基处理细胞的吸光度,A空白是空白培养基的吸光度。
2.5 细胞凋亡实验
将HeLa细胞接种3×105个细胞于6孔板上,培养24 h贴壁,弃去培养液,PBS轻轻冲洗细胞2次,设置正常对照组、PTX/TPGS-CR PMs(10 nmol·mL-1)组,每组设置3个复孔,每孔加入含药和非含药完全培养基2.5 mL。继续培养,作用时间截止后进行凋亡测定。操作步骤如下:分别收集各复孔上清液,用PBS清洗后再次收集,加不含乙二胺四乙酸(EDTA)的质量分数0.25%胰蛋白酶消化并收集,用4 ℃ PBS洗涤3遍。每管加200 μL预冷的1×Binding Buffer,重悬细胞。加入Annexin V-FITC后加入碘化丙啶(propidum iodide,PI)工作液(各5 μL),小心混匀。室温条件下避光染色15 min。加入300 μL 1×Binding Buffer,混匀后,过200目细胞筛网,移入流式管,立即上机检测。
2.6 细胞周期实验
将3×105个HeLa细胞接种于6孔板上,培养24 h,PBS冲洗细胞2遍,分别加入完全培养基、Taxol®、PTX/TPGS-CR PMs(PTX浓度为0.2 nmol·mL-1)培养,每孔2 mL,每组平行3份。收集各培养液,消化收集到离心管中,4 ℃ PBS重悬清洗2次,体积分数70%冷乙醇0.5 mL固定过夜,2 000 r·min-1离心4 min,经4 ℃ PBS清洗3次,用细胞周期检测试剂盒进行染色,避光孵育1 h,流式细胞仪测不同组别和处理时间对细胞周期的影响,Modfit 5.0软件分析实验数据。
2.7 细胞划痕实验
取对数期生长的迁移作用较强的4T1、HeLa细胞,分别接种3×105个细胞于6孔板中,每组3个复孔,每孔含培养基2.5 mL,至细胞分布均匀。将6孔板于培养箱中培养24 h(此时细胞密度应大于90%)。24 h后弃上清,清洗2遍,200 μL枪头沿6孔板底部十字标记,垂直于底部快速划出空白划痕带,每孔划痕枪头尽量使用同一枪头,用PBS清洗3遍洗去刮下的细胞,并在倒置显微镜下检查划痕处是否清洗干净。设置对照组、PTX/TPGS-CR PMs(10 nmol·mL-1)组,每孔加含药和不含药空白培养基2.5 mL以避免由于细胞增殖导致的迁移假象。置于倒置显微镜下进行0 h的拍照(×100)。拍照完毕后放入培养箱中培养,24 和48 h后于倒置显微镜下进行观察拍照。
3 结果
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3.1 PTX含量测定方法的建立
PTX含量的测定按“2.1.1”项下条件分析。以APTX与ADTX的比值(Y)对释放介质中PTX的质量浓度(ρ,μg·mL-1)作图,得回归方程为Y=0.061 2ρ+0.226(r2=0.999),结果表明,PTX在1~20 μg·mL-1范围内线性关系良好。
低、中、高3种浓度的PTX样品的日内精密度分别为(2.06±0.04) (5.02±0.06)及(10.04±0.19),相对标准偏差(RSD)分别为1.94%、1.16%及1.89%;日间精密度分别为(2.08±0.03) (5.06±0.06)及(9.97±0.18),RSD分别为1.54%、1.25%及1.81%;RSD均<2%,表明该方法日内、日间精密度良好。
低、中、高3种浓度的PTX样品的回收率分别为(99.28±1.28)%、(99.08±1.88)%以及(99.02±1.97)%,RSD分别为1.29%、1.90%及1.99%。
上述实验数据表明,PTX含量测定符合方法学要求。
3.2 体外释放实验
PTX/TPGS-CR PMs及Taxol®在不同释放介质中的释放曲线见图1。实验结果显示,在pH值7.4 PBS中,Taxol®释药速度较快,12 h时已释放71.45%,24 h累计释放率达到80%以上。由于Taxol®中PTX处于游离状态,且其相对分子质量较小,可以自由通过透析袋,因而快速释药并达到平衡状态。而PTX/TPGS-CR PMs 12 h释放50.84%,72 h内累积释放71.38%,PTX/TPGS-CR PMs中药物释放速度显著慢于Taxol®。说明PTX/TPGS-CR PMs在模拟血液环境pH条件下有一定的缓释特征,该缓释行为有利于递送PTX至肿瘤部位,减少PTX对正常组织的损伤。
PTX/TPGS-CR PMs在模拟肿瘤微环境的pH值5.8 PBS中释放较快。数据显示,12 h PTX累积释放了79.19%,72 h基本释放完全,呈现速释的效果。推测PTX/TPGS-CR PMs在体内达到肿瘤微环境后,快速释药,能使PTX更好地发挥抗肿瘤作用。而模拟肿瘤溶酶体内环境的pH值4.5 PBS中,PTX/TPGS-CR PMs 36 h内释放速度较缓,其中,12 h仅释放26.9%,其原因有待进一步研究。
用Origin软件对体外释药数据进行零级、一级、Higuchi、Weibull模型拟合结果见表1。Taxol®在pH值7.4 PBS和PTX/TPGS-CR PMs在pH 7.4、5.8、4.5 PBS中的释放动力学模型皆以Weibull模型拟合效果最好(表1),r2分别0.991、0.972、0.980及0.990。
3.3 细胞毒性实验
TPGS-CR偶联物与PTX/TPGS-CR PMs对4T1细胞的细胞毒结果见图2。等于或高于与PTX 10 nmol·mL-1对应的溶剂浓度的混合溶剂组,随着时间的延长细胞存活率急剧下降,存活率低。而TPGS-CR偶联物在48 h内对4T1细胞的存活率并没有显著影响,细胞存活率均在90%以上;相对于蓖麻油聚氧乙烯醚 的强非特异细胞毒性相比,TPGS-CR偶联物具有较好的安全性。随着TPGS-CR偶联物浓度进一步升高及作用时间的延长,72 h时,与PTX 50 nmol·mL-1对应浓度的TPGS-CR偶联物在4T1细胞上显示出一定程度的细胞增殖抑制效果(72 h抑制率为32.31%)。说明随作用时间的延长,TPGS-CR偶联物也能够发挥一定的抗肿瘤作用,有助于所包载的PTX杀伤肿瘤细胞。
Taxol®和PTX/TPGS-CR PMs均对4T1细胞有一定的抑制增殖作用,并随作用时间延长抑制能力增强,同时呈现浓度依赖性抑制作用效果。72 h时,Taxol®和PTX/TPGS-CR PMs对4T1细胞的半抵制浓度(IC50)分别为0.257 3和0.321 9 nmol·mL-1,表明Taxol®及PTX/TPGS-CR PMs对4T1细胞皆具有良好的杀伤作用。在实验测试浓度范围内,大于PTX 5 nmol·mL-1时,Taxol®的肿瘤杀伤作用很大程度上是由于其增溶剂蓖麻油聚氧乙烯醚 引起的,这也是Taxol®常引起不良反应的原因。而PTX/TPGS-CR PMs的细胞杀伤作用在48 h内及低于PTX 10 nmol·mL-1的72 h内与TPGS-CR偶联物无关。TPGS-CR偶联物的安全性决定了其形成的胶束包载并在体内递送PTX时,能减少PTX对机体的毒副作用。
3.4 细胞凋亡实验
流式细胞仪检测PTX/TPGS-CR PMs对HeLa、4T1细胞的凋亡影响,结果见图3。左上限为物理损伤细胞,左下限为正常细胞,右上限为晚凋细胞,右下限为早凋细胞。PTX/TPGS-CR PMs对HeLa、4T1细胞凋亡率的影响见表2。PTX/TPGS-CR PMs浓度为10 nmol·mL-1时,HeLa、4T1细胞凋亡率随着作用时间延长逐渐增加。HeLa细胞的存活率与凋亡率相关[14],可见PTX/TPGS-CR PMs对HeLa细胞的抑制作用主要是通过引起HeLa发生凋亡实现的。结合上述4T1细胞毒实验,PTX/TPGS-CR PMs对4T1细胞的杀伤作用在一定程度上与其影响了4T1细胞凋亡有关。
3.5 细胞周期实验
流式细胞仪检测各制剂作用于HeLa细胞后的细胞周期检测结果见图4,表3。可见,0.2 nmol·mL-1 PTX浓度下,PTX/TPGS-CR PMs和Taxol®使HeLa细胞的细胞产生了明显的变化,Control组的细胞周期主要分布在G0/G1期。两组制剂均能使更多细胞阻滞于G2/M期,抑制作用随时间延长而更加明显。与Taxol®相比,PTX/TPGS-CR PMs还能使较多细胞阻滞于G0/G1期,可能由于载体材料中大黄酸具有阻滞细胞于G0/G1期作用[15]。由此可见,TPGS-CR PMs与PTX能共同阻滞细胞周期,从而共同抑制肿瘤细胞有丝分裂,促进早期凋亡。
3.6 细胞划痕实验结果
划痕试验结果显示见图5,24、48 h后HeLa细胞空白组划痕距离均有缩短,PTX/TPGS-CR PMs干预的细胞划痕间距的缩短程度弱于空白组,表明10 nmol·mL-1 PTX/TPGS-CR PMs对HeLa细胞的迁移有抑制效果。PTX/TPGS-CR PMs对肿瘤细胞迁移的抑制将减少肿瘤细胞在体内的转移,有利于抗肿瘤的治疗。
不同浓度的PTX/TPGS-CR PMs抑制4T1细胞迁移的结果见图6,24 h时,空白对照组的划痕距离明显缩短,48 h时划痕几乎愈合;不同浓度的PTX/TPGS-CR PMs使划痕间距的缩短程度远小于空白对照组;随着剂量增大,划痕间距变化越来越小。结果表明,PTX/TPGS-CR PMs对4T1细胞的迁移能力有明显的抑制作用,并具有浓度依赖性。推测随着PTX/TPGS-CR PMs在体内肿瘤部位的累积,将更能够减少肿瘤转移的情况的发生。
4 讨论
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本研究采用pH 7.4、5.8、4.5 PBS作为释放介质,模拟正常血液、肿瘤微环境、肿瘤溶酶体环境的pH,对PTX/TPGS-CR PMs的体外释放行为进行了研究。在体外释放介质中加入0.8 mol·L-1水杨酸钠作为增溶剂,以达到漏槽条件[16-18]。体外释放实验前,将PTX/TPGS-CR PMs(1 mg·mL-1)分别置于37 ℃以上3种体外释放介质中,考察了其稳定性。结果显示,PTX/TPGS-CR PMs在水中粒径为(194.8±4.5) nm,在pH 7.4、5.8、4.5 PBS(含0.8 mol·L-1水杨酸钠)中放置后粒径逐渐变大,72 h后粒径分别为(265.6±3.9)(270.8±5.8)和 (261.1±7.5) nm,说明该胶束在3种介质中不会发生聚集,粒径变大可能与药物释放有关。
PTX/TPGS-CR PMs在3种介质中的体外释放行为表现出很好的pH响应释药特征,即其能在血液环境中缓释药物,既能减少药物对正常组织的损伤,又有利于将尽可能多的药物递送到肿瘤部位, 当其到达肿瘤微环境中能实现快速释药。从释放曲线可以看出,PTX/TPGS-CR PMs的在pH值7.4释放介质中的体外释放行为主要分为速释与缓释部分,速释部分所释放的药物,可能是吸附在胶束表面的游离药物分子,而包载于TPGS-CR胶束中的药物则以相对缓慢的释放速度从TPGS-CR PMs内核中释放出来。但对于其36 h内在pH 4.5 PBS中释放较在pH值7.4缓冲液中释放缓慢的表现,其原因需进一步深入研究。
TPGS-CR偶联物在48 h内对4T1细胞的存活率并没有显著影响,而在高浓度(50 nmol·mL-1)及长时间(72 h)作用时,呈现出一定程度的细胞增殖抑制效果的情况。细胞内存在大量酯酶[19],推测TPGS-CR偶联物可能在细胞内酯酶的作用下大黄酸和TPGS从该偶联物上断裂下来,对肿瘤细胞具有一定的杀伤作用,并将会协同药物发挥杀伤肿瘤细胞的作用。
PTX/TPGS-CR PMs的细胞毒性具有时间和浓度依赖性,其5 nmol·L-1浓度以下与Taxol®毒性大小相似,更大浓度时Taxol®毒性显示更强,但Taxol®的毒性很大程度上是由于其混合溶剂引起的,这也是Taxol®注射后引起毒副反应[20-21]的原因之一。TPGS-CR偶联物由于在48 h内几乎不显示毒性,且其形成的胶束将药物包载于内核中,胶束的细胞杀伤作用涉及胶束释放药物的过程。因此,PTX/TPGS-CR PMs的细胞毒具有时间依赖性特征。随着作用时间的延长,PTX/TPGS-CR PMs在肿瘤部位的不断累积,胶束中药物的不断释放,药物与载体材料的协同起效,PTX/TPGS-CR PMs能更好地起到杀伤肿瘤细胞的作用。
PTX/TPGS-CR PMs对HeLa、4T1细胞凋亡率也是随作用时间的延长而凋亡率增加,也与药物的不断释放,越来越多药物作用于肿瘤细胞有关,从而引起对肿瘤细胞毒性的增加。从PTX/TPGS-CR PMs对HeLa的细胞周期的影响上来看,与Taxol®对比分析,除了PTX对细胞周期的影响外,载体材料组成部分(如大黄酸)也可能起到了一定的作用,从而有助于促进细胞凋亡。PTX/TPGS-CR PMs在细胞划痕试验中所体现出的对不同细胞的抑制迁移作用以及浓度依赖性,也体现了该胶束能够较好地抑制肿瘤的转移,有利于肿瘤治疗。
综上,PTX/TPGS-CR PMs具有良好的pH响应释药的特征,在肿瘤微酸性环境下能实现快速释药从而提高抗肿瘤作用;在细胞水平上能实现提高抑瘤率,促进细胞凋亡,增加在G0/G1期的周期阻滞,减少肿瘤细胞迁移,这些作用在一定程度与其药物释放过程有关。本研究后续将结合该体外释放和细胞实验结果,进一步利用Balb/c小鼠建立4T1皮下移植瘤模型,进行PTX/TPGS-CR PMs抑制体内肿瘤生长和减少PTX毒性的药效学研究,以证实PTX/TPGS-CR PMs静脉注射给药后在体内抗肿瘤增效减毒的效果。
基金
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  • 国家自然科学基金项目(81603301)
  • 福建省科技厅引导性项目(2020Y0050)
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参考文献 引证文献
排序方式：
[1]
WANG X Y, ZHENG Y L, QIU L Z, et al. Evaluation and antitumor mechanism of functionalized chitosan-based polymeric micelles for oral delivery of paclitaxel[J]. Int J Pharm, 2022, 625: 122138. DOI:10.1016/j.ijpharm.2022.122138.
[2]
ZHAO Y, CAO W Q, LIU Y. Recent advances in polymeric nano-sized carrier systems[J]. Chem J Chin Univ(高等学校化学学报), 2020, 41(5): 909-923.
[3]
WU C Y, CHEN T K, WANG Q. Research progress of puerarin preparation[J]. World Chin Med(世界中医药), 2020, 15(14): 2188-2192.
[4]
ZHANG X, XU X Y, WANG X Y, et al. Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol[J]. Carbohydr Polym, 2023, 303: 120439. DOI:10.1016/j.carbpol.2022.120439.
[5]
WANG X Y, QIU L Z, WANG X Y. Evaluation of intestinal permeation enhancement with carboxymethyl chitosan-rhein polymeric micelles for oral delivery of paclitaxel[J]. Int J Pharm, 2020, 573: 118840. DOI:10.1016/j.ijpharm.2019.118840.
[6]
WANG X Y, GUO Y L, QIU L Z, et al. Preparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel[J]. Carbohydr Polym, 2019, 206: 121-131.
[7]
LI M, LIU Y, GONG H. Preparation and performance study of carboxymethyl chitosan composite hydrogels[J]. Chin J Mar Drugs(中国海洋药物杂志), 2022, 41(2): 19-27.
[8]
PEI D T, ZENG Z W, ZHOU X Y. Preparation and characterization of carboxymethyl chitosan/glucose hydrogel in situ cross-linked by enzyme[J]. Chem Res Appl(化学研究与应用), 2022, 34(5): 1061-1069.
[9]
WANG X Y, QIU L Z, LI Q Z, et al. Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles[J]. J China Pharm Univ(中国药科大学学报), 2018, 49(5): 596-602.
[10]
JIANG L, YANG Y. Research progress on antitumor mechanism of rhubaric acid[J]. Chin Tradit Pat Med(中成药), 2021, 43(10): 2765-2769.
[11]
GUO Y Y, LUO J, TAN S W, et al. The applications of vitamin E TPGS in drug delivery[J]. Eur J Pharm Sci, 2013, 49(2): 175-186.
[12]
GUO Y, CHU M, TAN S, et al. Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance[J]. Mol Pharm, 2014, 11(1): 59-70.
[13]
QIU L Z, WANG X Y, CAO C X, et al. Preparation and characterization of TPGS modified carboxymethyl chitosan-rhein polymeric micelles[J]. J Shenyang Pharm Univ(沈阳药科大学学报), 2019, 36(4): 300-307.
[14]
OUYANG H Z, QIU L Z, WANG X Y, et al. Preparation and preliminary evaluation of paclitaxel-loaded TPGS-CR polymeric micelles[J]. Chin Pharm J(中国药学杂志), 2020, 55(7): 534-541.
[15]
SHU L, JIAO W, TING S, et al. The natural agent rhein induces beta-catenin degradation and tumour growth arrest[J]. J Cell Mol Med, 2018, 22(1): 589-599.
[16]
ZHANG Z R. Synthesis and characterization of PLGA copolymer and antitumor activity and mechanism of paclitaxel-containing microspheres[D]. Wuhan: Wuhan University of Technology, 2018.
[17]
CHEN Z, LI L B. Preparation and in vitro Evaluation of Novel Paclitaxel-Loaded Liposomes[J]. Pharm Biotechnol(药物生物技术), 2018, 25(2): 108-113.
[18]
XU C. Construction of co-loaded paclitaxel and siRNA-E7 nanodelivery system encapsulated by HeLa cell membrane and its therapeutic effect on cervical cancer[D]. Shanghai: Shanghai Jiao Tong University, 2020.
[19]
YIN Y G, KONG X Q, LI M, et al. Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples[J]. Anal Chim Acta, 2022, 1190: 339248. DOI:10.1016/j.aca.2021.339248.
[20]
ZHAO Y. Clinical adverse drug reactions of paclitaxel for injection (albumin binding type)[J]. Chin Pract Med(中国实用医药), 2021, 16(15): 137-139.
[21]
WANG Y W, MENG L, LIU X. ADR signal mining of paclitaxel for injection(albumin-bound type) based on FDA adverse event database[J]. J China Pharm(中国药房), 2021, 32(3): 328-333.
2024年第59卷第15期
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doi: 10.11669/cpj.2024.15.007
  • 接收时间：2023-03-05
  • 首发时间：2026-01-14
  • 出版时间：2024-08-08
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  • 收稿日期：2023-03-05
基金
国家自然科学基金项目(81603301)
福建省科技厅引导性项目(2020Y0050)
作者信息
    福建中医药大学药学院, 福州 350122

通讯作者:

* 王晓颖,女,博士,教授,硕士生导师 研究方向:缓控释及靶向药物制剂研究 Tel:(0291)22861135;
徐伟,男,博士,教授,博士生导师 研究方向:中药药效物质基础及作用机制研究 Tel:(0591)22861693
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
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光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
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