肿瘤药学2025，Vol.15Issue(2)：178-186,9.DOI:10.3969/j.issn.2095-1264.2025.02.05
一种新型克唑替尼纳米药物制剂的制备及其体外抗非小细胞肺癌研究
Design and development of a novel crizotinib nanoformulation:in vitro investigation of its antitumor efficacy against non-small cell lung cancer
摘要
Abstract
Objective To develop a hyaluronic acid(HA)-modified crizotinib(Cri)nanoparticle drug delivery system (HDC NPs)to address the poor water solubility and low bioavailability of Cri,while endowing it with properties of pH-re-sponsive controlled release,active targeting and long circulating,so as to provide a novel strategy for precise treatment of non-small cell lung cancer(NSCLC).Methods Using 3,3'-dithiodipropionic acid(DTPA)as a linker,HA and Cri were co-valently conjugated via amidation reaction to synthesize the amphiphilic polymer HA-DTPA-Cri(HDC),followed by self-as-sembly to prepare HDC NPs.The structure of the polymer was verified using Fourier transform infrared spectroscopy(FTIR)and proton nuclear magnetic resonance(¹H-NMR).Dynamic light scattering(DLS)was employed to determine the particle size and zeta potential,while transmission electron microscopy(TEM)was used to observe nanoparticle morphology.Ultravio-let spectrophotometry was used to determine drug loading(DL)and encapsulation efficiency(EE).In vitro release behavior(pH 7.4 vs.5.0)was evaluated via dialysis.Flow cytometry and confocal microscopy were used to analyze the cellular uptake efficiency in A549 cells,while cytotoxicity assay(MTT method)to assess the antitumor activity.Results The HDC polymer was successfully synthesized.By optimizing the ratio of hydrophilic to hydrophobic materials,various HDC NPs with differ-ent sizes were prepared.When the mass ratio of HA-DTPA(HD)to Cri is 1:1,the nanoparticles exhibited a size of(215.97±10.12)nm,a zeta potential of(-17.23±0.98)mV,and a polydispersity index(PDI)of(0.197±0.048).Observation of nanoparticles as uniform spherical shapes through TEM.The nanodrug formulation prepared at this ratio has a drug load-ing capacity of(3.55±0.48)％and an encapsulation efficiency of(42.61±3.96)％.In vitro release studies showed that HDC NPs exhibited sustained release properties and pH-responsive controlled release under acidic conditions(pH 5.0),with a 72-hour release rate of(73.28±1.88)％.Cellular experiments using A549 cells as an NSCLC model showed that HDC NPs achieved a cellular uptake rate of(28.12±0.66)％,significantly higher than free Cri,and exhibited enhanced inhibition of tu-mor cell proliferation and viability.Conclusion The newly developed HDC NPs exhibit uniform size,well-defined morphol-ogy,excellent dispersibility,and stability.They enable sustained and controlled release and demonstrate superior antitumor efficacy in vitro.This study provides a promising strategy for the improvement of crizotinib formulations and targeted thera-py for NSCLC.关键词
非小细胞肺癌/克唑替尼/纳米制剂/靶向递送系统/透明质酸Key words
NSCLC/Crizotinib/Nanoformulation/Targeted delivery system/Hyaluronic acid分类
医药卫生引用本文复制引用
刘泓池,罗迁,刘熠,阳仪,陶晓军,袁立明..一种新型克唑替尼纳米药物制剂的制备及其体外抗非小细胞肺癌研究[J].肿瘤药学,2025,15(2):178-186,9.基金项目
湖南省研究生创新科研项目(CX20230532) （CX20230532）
湖南省大学生创新训练计划项目(S202410542134S) （S202410542134S）
湖南师范大学大学生创新创业训练计划项目(S202410542233). （S202410542233）
