Article(id=1236700469268107545, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236700465119949418, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1658419200000, acceptedDateStr=2022-07-22, onlineDate=1772781968656, onlineDateStr=2026-03-06, pubDate=1681488000000, pubDateStr=2023-04-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772781968656, onlineIssueDateStr=2026-03-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772781968656, creator=13701087609, updateTime=1772781968656, updator=13701087609, issue=Issue{id=1236700465119949418, tenantId=1146029695717560320, journalId=1235980733773295621, year='2023', volume='32', issue='7', pageStart='657', pageEnd='760', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1772781967668, creator=13701087609, updateTime=1772782901622, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236704382474047808, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236700465119949418, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236704382474047809, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236700465119949418, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=728, endPage=734, ext={EN=ArticleExt(id=1236700469494599975, articleId=1236700469268107545, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Pharmacodynamics and tissue distribution of paclitaxel saturated fatty acid ester liposomes, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=

Objective: Three kinds of paclitaxel saturated fatty acid ester liposomes were prepared to preliminarily compare the difference between them in anti-tumor, and to explore the reasons for the difference of efficacy by the study of tissue distribution.Methods:Three kinds of paclitaxel fatty acid ester liposomes were prepared by thin film dispersion method, and the particle size, potential, encapsulation efficiency and drug loading were measured, respectively. A mouse model of breast cancer was established, and paclitaxel injection (Taxol), paclitaxel myristate liposome (PTX-MA-L), paclitaxel palmitate liposome (PTX-PA-L) and paclitaxel stearate liposome (PTX-SA-L) were injected via the tail vein, respectively. The anti-tumor effects of the two preparations were investigated, and the safety of the preparations was evaluated by routine blood tests. Finally, the prodrug metabolism for three prodrug liposomes was evaluated by in vivo tissue distribution.Results:Three taxol saturated fatty acid ester liposomes were successfully constructed. The particle sizes of PTX-MA-L, PTX-PA-L and PTX-SA-L are (69.56±1.08), (72±0.86) and (75±1.02) nm; Polymer dispersity index (PDI) are (0.185±0.009), (0.165±0.012), (0.171±0.024); Zeta potentials are -(11.26±1.37), -(12.18±1.86), -(13.92±0.59) mV, respectively. Encapsulation rates are (95±0.39)%, (97±0.28)% and (98±0.19)%, respectively. In pharmacodynamic evaluation in 4T1 breast cancer transplanted tumor model, the pharmacodynamic of PTX-PA-L at equal dose was stronger than that of taxol, PTX-MA-L and PTX-SA-L. The results of routine blood test showed that the blood cell level of paclitaxel fatty acid ester liposome was significantly higher than that of paclitaxel injection. The tissue distribution results showed that PTX-MA-L was metabolized to PTX at a fast rate, short half-life and fast elimination rate. PTX metabolized from PTX-PA-L increases slowly with time. Its half-life is the longest among the three prodrug liposomes, the area under the drug-time curve is the largest, and the clearance rate is the lowest. PTX-SA-L was metabolized to PTX the most slowly, and the maximum plasma concentration was the lowest in tumors.Conclusion:The paclitaxel prodrug liposome modified with saturated fatty acid has better tumor treatment effect and alleviates the toxic and side effects caused by traditional paclitaxel dosage forms. Among them, the antitumor effect of PTX-PA-L is better than that of PTX-MA-L and PTX-SA-L, which may be related to the metabolism of fatty acid prodrugs in vivo.

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目的：制备3种紫杉醇（PTX）饱和长链脂肪酸酯脂质体，初步比较3种紫杉醇饱和脂肪酸酯脂质体在抗肿瘤方面的差异，通过组织分布研究，探讨造成疗效差异的原因。方法：采用薄膜分散法制备3种紫杉醇脂肪酸酯脂质体，分别测定粒径、Zeta电位、包封率以及载药量情况；构建小鼠乳腺癌模型，尾静脉分别注射紫杉醇注射液（Taxol^®）、紫杉醇肉豆蔻酸酯脂质体（PTX-MA-L）、紫杉醇棕榈酸酯脂质体（PTX-PA-L）和紫杉醇硬脂酸酯脂质体（PTX-SA-L），考察它们的抗肿瘤效果，同时通过血常规检测对制剂的安全性进行初步评价。最后，对3种前药脂质体进行体内组织分布实验，考察前药代谢情况。结果：成功构建了3种紫杉醇饱和脂肪酸酯脂质体，PTX-MA-L，PTX-PA-L，PTX-SA-L的粒径分别为（69.56±1.08），（72±0.86），（75±1.02） nm，聚合物分散性指数（PDI）分别为（0.185±0.009），（0.165±0.012），（0.171±0.024），Zeta电位分别为-（11.26±1.37），-（12.18±1.86），-（13.92±0.59） mV，包封率分别为（95±0.39）%，（97±0.28）%，（98±0.19）%。4T1乳腺癌移植瘤模型药效评价中，等剂量下PTX-PA-L的药效好于Taxol，PTX-MA-L和PTX-SA-L。血常规检测结果表明，紫杉醇脂肪酸酯脂质体的血细胞水平明显高于紫杉醇注射液。组织分布实验结果显示，PTX-MA-L代谢出的PTX速率最快，半衰期短，消除率快；PTX-PA-L代谢出的PTX随时间缓慢增加，半衰期在3种前药脂质体中最长，AUC最大，清除率最慢；PTX-SA-L代谢出的PTX最慢，在肿瘤中最大血药浓度最小。结论：饱和脂肪酸修饰的紫杉醇前药脂质体有较好的抗肿瘤疗效，能减轻传统紫杉醇剂型带来的不良反应。其中PTX-PA-L的抗肿瘤效果优于PTX-MA-L和PTX-SA-L，这与脂肪酸前药在体内的代谢有关。

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韦武豪，男，硕士研究生，主要从事纳米给药系统研究。联系电话：(021)31198949，E-mail: Weisty_0324@163.com。

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韦武豪，男，硕士研究生，主要从事纳米给药系统研究。联系电话：(021)31198949，E-mail: Weisty_0324@163.com。

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