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林产化学与工业 ›› 2019, Vol. 39 ›› Issue (2): 25-32.doi: 10.3969/j.issn.0253-2417.2019.02.004

• 研究报告 • 上一篇    下一篇

漆酚/两亲共聚物mPEG-PBAE胶束的pH响应性及其体外性能

周昊1,2,齐志文1,2,马余璐1,2,王成章1,2,*   

  1. 1. 中国林业科学研究院 林产化学工业研究所;生物质化学利用国家工程实验室;国家林业局 林产化学工程重点开放性实验室;江苏省 生物质能源与材料重点实验室,江苏 南京 210042
    2. 南京林业大学 江苏省林业资源高效加工利用协同创新中心,江苏 南京 210037
  • 收稿日期:2018-11-30 出版日期:2019-04-25 发布日期:2019-05-08
  • 通讯作者: 王成章
  • 作者简介:周昊(1982—),女,江苏盐城人,副研究员,硕士,主要从事天然产物化学与利用研究
  • 基金资助:
    国家自然科学基金资助项目(31600467)

pH Responsiveness and in vitro Performance of Urushiol/Amphiphilic Copolymer mPEG-PBAE Micelles

Hao ZHOU1,2,Zhiwen QI1,2,Yulu MA1,2,Chengzhang WANG1,2,*   

  1. 1. Institute of Chemical Industry of Forest Products, CAF; National Engineering Lab. for Biomass Chemical Utilization; Key and Open Lab. of Forest Chemical Engineering, SFA; Key Lab. of Biomass Energy and Material, Jiangsu Province, Nanjing 210042, China
    2. Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, China
  • Received:2018-11-30 Online:2019-04-25 Published:2019-05-08
  • Contact: Chengzhang WANG
  • Supported by:
    国家自然科学基金资助项目(31600467)

摘要:

以末端带氨基的甲氧基聚乙二醇(mPEG-NH2)、十四胺、5-氨基-1-戊醇、1, 4-丁二醇二丙烯酸酯和1, 3-戊二胺为原料,采用一锅法合成了一种两亲共聚物聚乙二醇-聚β-氨基酯(mPEG-PBAE),通过FT-IR、GPC、芘荧光探针对聚合物的结构、相对分子质量和临界胶束浓度(CCMC)进行了表征;以漆酚为药物模型分子,采用透析法制备了漆酚/两亲共聚物胶束,采用TEM和DLS对载药胶束的粒径、Zeta电位、形貌进行了表征,考察了载药胶束的pH响应性、体外释药性和体外抗肿瘤活性。研究结果表明:两亲共聚物mPEG-PBAE已经成功合成,重均相对分子质量为11 445,与设计的理论相对分子质量相差不大,聚合物的CCMC值为18.25 mg/L;制备得到的漆酚/两亲共聚物胶束的包封率为82.29%,载药量为23.21%,外观呈规则球形结构,大小均一,平均粒径为160.1 nm,Zeta电位值为33.6 mV,其在pH值为5.0的缓冲溶液中粒径增大明显高于pH值为6.5和7.4的缓冲溶液,具有明显的pH响应性;当pH值为5.0、6.5和7.4时,72 h内累计释药率分别为98.7%、61.6%和31.5%;载药胶束对HepG2和A549肿瘤细胞的半数抑制浓度(IC50)分别为1.38和0.87 mg/L,体外抗肿瘤活性明显优于游离漆酚。

关键词: 漆酚, pH响应性, 两亲共聚物胶束, 抗肿瘤

Abstract:

With methoxy polyethylene glycol with terminal amino group (mPEG-NH2), tetradecyl amine, 5-amino-1-pentanol, 1, 4-butanediol diacrylate and 1, 3-pentanediamine diacrylate as raw materials, the amphiphilic polymer poly (ethylene glycol)-poly (β-amino) ester (mPEG-PBAE) was synthesized by one-pot method. The structure, molecular weight and CMC of the amphiphilic polymer (mPEG-PBAE) were characterized by FT-IR, GPC and pyrene fluorescence probe. Using urushiol as the drug model molecule, the mPEG-PBAE polymer micelles loaded with urushiol were prepared by dialysis method. The particle size, Zeta potential and morphology of the micelles loaded with urushiol were characterized by TEM and DLS. The pH responsiveness, drug release and its in vitro antitumor activity were investigated. The results showed that the amphiphilic copolymer mPEG-PBAE was successfully prepared and the weight average relative molecular mass was 11 445, which was not significantly different from the designed theoretical relative molecular mass, the CMC value of the polymer was 18.25 mg/L. The entrapment efficiency was 82.29% and drug loading capacity was 23.21%, the appearance of drug loaded micelles was regular spherical structure, the size was uniform, and the average particle size was 160.1 nm. The Zeta potential value of drug loaded micelles was 33.6 mV, its particle size in the buffer solution of pH value 5.0 was significantly higher than that in solution of pH value 6.5 and 7.4, and had obvious pH responsiveness. When pH value was 5.0, the cumulative drug release rate in 72 h was 98.7%; when pH value was 6.5 and 7.4, the cumulative drug release rates in 72 h were 61.6% and 31.5%, respectively. The median inhibitory concentrations (IC50) of the drug loaded micelles on HepG2 and A549 tumor cells were 1.38 and 0.87 mg/L, respectively; which showed better in vitro antitumor activity than that of free urushiol.

Key words: urushiol, pH responsiveness, amphiphilic copolymer micelle, antitumor

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