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透明质酸修饰的载大黄素多壁碳纳米管递药系统的制备及对乳

          腺癌细胞的抑制作用研究
                                                 Δ


          李瑜多 ,杜 娟 ,刘云龙,耿 峰,陈小兵(齐齐哈尔医学院附属第二医院药学部临床药学室,黑龙江 齐齐哈尔
                *
                         #
          161000)

          中图分类号  R94;R737.9      文献标志码  A      文章编号  1001-0408(2025)12-1463-07
          DOI  10.6039/j.issn.1001-0408.2025.12.08


          摘  要  目的  制备透明质酸(HA)修饰的负载大黄素(EMD)的多壁碳纳米管(MWCNTs)递药系统(HA-MWCNTs-EMD),并研
          究其对乳腺癌细胞的体外抑制作用。方法  将EMD负载于MWCNTs,制得递药系统MWCNTs-EMD;进一步以HA进行修饰,制
          得递药系统HA-MWCNTs-EMD;对上述两种递药系统进行表征。以游离EMD为参照,考察上述两种递药系统的体外释药情况,
          检测两种乳腺癌细胞(MCF-7、MDA-MB-231细胞)对系统中EMD的摄取情况,并检测两种递药系统对两种乳腺癌细胞表面糖蛋
          白分化群44(CD44)表达、活力、凋亡、乳酸脱氢酶(LDH)释放量的影响。结果  MWCNTs-EMD、HA-MWCNTs-EMD的包封率均
          为(63.52±2.74)%,载药量分别为(25.01±1.83)%、(12.13±1.96)%,粒径分别为(865.95±2.16)、(351.86±1.68)nm,多分散性指
          数分别为0.54±0.02、0.23±0.01,Zeta电位分别为(23.87±0.14)、(-42.79±0.39)mV。MWCNTs-EMD、HA-MWCNTs-EMD在2、
          4、6、8、10、12、24 h 时的 EMD 累积释放量均显著低于同期游离 EMD,而 HA-MWCNTs-EMD 显著高于同期 MWCNTs-EMD(P<
          0.05);两种乳腺癌细胞对MWCNTs-EMD、HA-MWCNTs-EMD中EMD的摄取量均显著高于其对游离EMD的摄取量(P<0.05);
          与游离 EMD 组比较,MWCNTs-EMD、HA-MWCNTs-EMD 组两种细胞的凋亡率、LDH 释放量均显著升高,表面 CD44 的表达
         (MWCNTs-EMD 组除外)、细胞活力均显著下调或降低,且 HA-MWCNTs-EMD 的作用更显著(P<0.05)。结论  成功制备负载
          EMD 的新型递药系统 HA-MWCNTs-EMD;该递药系统具有一定的缓释作用,可明显降低乳腺癌细胞活力,促进其凋亡并增加
          LDH释放,且上述抗乳腺癌作用明显强于游离EMD和MWCNTs-EMD。
          关键词  大黄素;多壁碳纳米管;透明质酸;递药系统;乳腺癌;抑制作用


          Preparation of HA-modified emodin-contained multi-walled carbon nanotubes drug delivery system and its
          inhibitory effect on breast cancer cells
          LI Yuduo,DU Juan,LIU Yunlong,GENG Feng,CHEN Xiaobing(Dept.  of  Clinical  Pharmacy,  the  Second
          Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjiang 161000, China)

          ABSTRACT   OBJECTIVE  To  prepare  hyaluronic  acid (HA)-modified  emodin (EMD)-contained  multi-walled  carbon  nanotubes
         (MWCNTs)  drug  delivery  system (HA-MWCNTs-EMD)  and  explore  its  in  vitro  inhibitory  effect  on  breast  cancer  cells.
          METHODS  EMD  was  loaded  onto  MWCNTs  to  prepare  a  drug  delivery  system  MWCNTs-EMD;  subsequently,  the  system  was
          further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above
          were  characterized.  With  free  EMD  as  the  reference,  the  drug  release  in  vitro  of  the  above  two  drug  delivery  systems  was
          investigated; the uptake of EMD by two breast cancer cells (MCF-7, MDA-MB-231 cells) was detected. The impacts of the above
          two  drug  delivery  systems  on  the  expression  of  surface  glycoprotein  differentiation  group  44 (CD44),  activity,  apoptosis  and
          lactate  dehydrogenase (LDH)  release  of  two  breast  cancer  cells  were  detected.  RESULTS  The  encapsulation  efficiencies  of
          MWCNTs-EMD  and  HA-MWCNTs-EMD  were  both (63.52±2.74)%,  with  drug  loading  rates  of (25.01±1.83)%  and (12.13±
          1.96)%, particle sizes of (865.95±2.16) and (351.86±1.68) nm, polydispersity indexes of 0.54±0.02 and 0.23±0.01, and Zeta
          potentials of (23.87±0.14) and (-42.79±0.39) mV, respectively. The 2, 4, 6, 8, 10, 12 and 24-hour cumulative release rates
                                                             of  EMD  in  MWCNTs-EMD  and  HA-MWCNTs-EMD  were
             Δ 基金项目 黑龙江省省属高等学校基本科研业务费科研项目
         (No.2022-KYYWF-0785)                                significantly  lower  than  those  in  free  EMD,  while  the
             *第一作者 主管药师。研究方向:药理学。E-mail:lydiacz@163.         cumulative   release   rate   of   HA-MWCNTs-EMD   was
          com
                                                             significantly  higher  than  that  of  MWCNTs-EMD (P<0.05);
             # 通信作者 副主任药师。研究方向:临床药学、药剂学。E-mail:
          22647357@qq.com                                    the  EMD  uptakes  of  MWCNTs-EMD  and  HA-MWCNTs-EMD


          中国药房  2025年第36卷第12期                                              China Pharmacy  2025 Vol. 36  No. 12    · 1463 ·
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