透明质酸修饰的载阿霉素多壁碳纳米管递药系统的制备及体外评价

Preparation of a hyaluronic acid-modified doxorubicin-loaded multi-walled carbon nanotubes drug delivery system and its in vitro evaluation

目的:制备透明质酸修饰的载阿霉素多壁碳纳米管主动靶向递药系统,并考察其对乳腺癌的抑制作用。方法:将阿霉素(DOX)通过π-π键相互作用负载于氨基化多壁碳纳米管(NH2-MCNTs)上,构建被动递药系统(DOX-MCNTs);使用透明质酸(HA)对DOX-MCNTs进行修饰,构建主动靶向递药系统(HADOX-MCNTs)。对递药系统的粒径及Zeta电位、包封率、载药量及体外释放等进行了考察,采用人乳腺癌MDA-MB-231细胞进行了体外细胞摄取、细胞毒性和细胞划痕愈合评价。结果:HA-DOX-MCNTs的平均粒径为(349. 9±1. 5) nm;DOX-MCNTs对阿霉素的包封率为61. 2%,载药量为23. 4%;DOX-MCNTs经HA修饰后,DOX的释放量随着时间的延长持续提高,24 h释放率达到28. 6%;与DOX-MCNTs组相比,HA-DOXMCNTs组细胞摄取DOX的量更多;HA-DOX-MCNTs的细胞毒作用是DOX-MCNTs的3. 78倍;HA-DOX-MCNTs能够显著降低MDA-MB-231细胞的迁移能力。结论:HA修饰的载阿霉素多壁碳纳米管靶向递药系统制备成功,有用于肿瘤靶向治疗的潜力。

Objective:To develop a hyaluronic acid(HA)-modified doxorubicin(DOX)-loaded active targeting drug delivery system(HA-DOX-MCNTs)and investigate its inhibitory effect on breast cancer cells.Methods:DOX was loaded into the amino multi-walled carbon nanotubes(NH2-MCNTs)byπ-πstacking interactions to construct a passive targeting drug delivery system(DOX-MCNTs).Then,HA was used to modify DOX-MCNTs to construct an active targeting drug delivery system(HA-DOX-MCNTs).The particle size and zeta potential,encapsulation efficiency,drug loading,and in vitro release profiles of HA-DOX-MCNTs were evaluated;assay of in vitro cellular uptake,cytotoxicity and wound healing of HA-DOX-MCNTs was performed on MDA-MB-231 cells.Results:The average particle size of HA-DOX-MCNTs was(349.9±1.5)nm.The encapsulation efficiency of DOX-MCNTs was 61.2%,and the drug-loading rate was 23.4%.The release rate of DOX from HA-DOX-MCNTs(28.6%within 24 h)was higher than that from DOX-MCNTs.Higher cellular uptake efficiency of DOX was observed in the HA-DOX-MCNTs group compared with DOX-MCNTs group.HA-DOX-MCNTs displayed 2.78 fold higher cytotoxicity than DOX-MCNTs against MDA-MB-231 cells in vitro.HA-DOX-MCNTs had stronger inhibitory effect on the migration of MDA-MB-231 cells than DOX-MCNTs.Conclusion:HA-modified DOX-loaded multiwalled carbon nanotube targeting drug delivery system has been successfully prepared,and it might be a potentialformulation for targeting cancer therapy.