摘要
目的:制备透明质酸(HA)修饰7-乙基-10-羟基喜树碱纳米混悬液(S1C1),探究其抗肿瘤治疗作用,为纳米制剂临床应用提供参考。方法:经电荷吸附法制备纳米混悬液(S1C1-HA);经动态光散射粒径仪进行制剂表征和粒径稳定性考察;运用高效液相色谱法(HPLC)测定S1C1-HA的包封率和载药量;采用噻唑蓝法考察游离纳米混悬液对4T1细胞的增殖抑制作用;运用3D多细胞肿瘤球考察纳米混悬剂的肿瘤球渗透力;通过考察纳米混悬液的体内药动学行为、脏器分布行为和抗肿瘤治疗,评价制剂的体内药效。结果:S1C1-HA平均粒径138.04 nm,电位-8.03 mV,体外24 h内粒径稳定性良好,载药量5.44%,包封率90.07%;S1C1半数抑制浓度为S1C1-HA的4.59倍,S1C1-HA的肿瘤渗透能力显著增强;S1C1-HA的半衰期和药时曲线下面积为S1C1的5.55,17.12倍,其体内抗肿瘤治疗效果显著增强。结论:修饰后S1C1-HA能显著增强药物的稳定性、细胞毒性、肿瘤渗透能力,有更优异的体内生物利用度和抗肿瘤治疗作用,S1C1-HA较S1C1更有临床应用潜力。
OBJECTIVE To prepare hyaluronic acid(HA) modified 7-ethyl-10-hydroxycamptothecin nanosuspension(S1 C1), investigate its antitumor therapeutic effect and provide reference for clinical application of nano-formulations.METHODS S1 C1-HA nanosuspension was prepared by charge adsorption;characterizations and particle size stability of S1 C1-HA were investigated by dynamic light scattering;the encapsulation efficiency and loading efficiency of S1 C1-HA were investigated by high performance liquid chromatography;the proliferation inhibitory effect on 4 T1 cells was inspected by MTT assay;the tumor penetration of nanosuspension was characterized by 3 D multicellular tumor spheroids;in vivo pharmacokinetic behavior and distribution of nanosuspension were researched and detected by LC-MS;anti-tumor therapeutic effect of the nanosuspension was studied in 4 T1 tumor-bearing mice model in vivo.RESULTS The average particle size and Zeta potential of S1 C1-HA respectively was 149.7 nm and-5.81 mV with good particle size stability within 24 h in vitro;the loading efficiency and encapsulation efficiency were 5.44% and 90.07%, respectively;the ICof S1 C1 was 2.32 times higher than that of S1 C1-HA. The tumor sphere penetration ability of S1 C1-HA was significantly enhanced;the half-life and AUC of S1 C1-HA were 5.55 and 17.12 times higher than those of S1 C1 in vivo;moreover, the antitumor therapeutic effect of S1 C1-HA was significantly enhanced for the introduction of HA.CONCLUSION The modified S1 C1-HA shows significantly enhanced particle stability, cytotoxicity, tumor penetration and antitumor therapeutic effects in vitro and in vivo. S1 C1-HA will be more potential for clinical application compared with S1 C1.
作者
杨琴
蒲前
王凯悦
龚涛
刘福
周春阳
罗荧萍
YANG Qin;PU Qian;WANG Kai-yue;GONG Tao;LIU Fu;ZHOU Chun-yang;LUO Ying-ping(School of Pharmacy,North Sichuan Medical College,Sichuan Nanchong 637000,China;West China School of Pharmacy,Sichuan University,Sichuan Chengdu 610041,China;Department of Pharmacy,Affiliated Hospital of North Sichuan Medical College,Sichuan Nanchong 637000,China)
出处
《中国医院药学杂志》
CAS
北大核心
2022年第15期1518-1522,1567,共6页
Chinese Journal of Hospital Pharmacy
基金
南充市2019年市校合作科研专项项目(编号:19SXHZ0445)
南充市2020年市校科技战略合作专项项目(编号:20SXQT0326)
川北医学院药学一流学科群(编号:CYB21-YLXK03)。
