In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated by desolvation method were chondroitin sulfate (CS) was used as the surface exposed ligand to achieve CD44 receptor mediated targeting of brain tumor. The developed CS-TNPs were characterized for particle size, zeta potential, entrapment efficiency and drug loading and evaluated by FTIR, DSC, XRD and TEM analysis. BBB (blood brain barrier) passage study using in vitro BBB model indicated that CS-TNPs were able to efficiently cross the BBB. Cell viability assay data demonstrated higher cytotoxicity of CS-TNPs as compared with pure TMZ. The CD44 receptor blocking assay and receptor poisoning assay in U87 MG cells confirmed the CD44 receptor and endocytosis-mediated (caveolae pathway) uptake of CS-TNPs. CS-TNPs were able to generate ROS in U87 MG cells. In vivo pharmacokinetic and biodistribution studies were performed in Wistar rats. In vivo results revealed significant enhancement in pharmacokinetic profile of CS-TNPs as compared with TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in the brain by CS-TNPs as compared with the pure drug that confirmed the brain targeting ability of nanoparticles. From all obtained results, it may be concluded that CS-TNPs are promising carrier to deliver TMZ to the brain for targeted therapy of brain tumor.

在本研究中，以硫酸软骨素（CS）为表面暴露配体，采用去溶剂法制备了载有替莫唑胺（TMZ）的硫酸软骨素共轭白蛋白纳米粒子（CS-TNPs），以实现CD44受体介导的脑肿瘤靶向。对所开发的 CS-TNPs 的粒径、zeta 电位、包封率和载药量进行了表征，并通过 FTIR、DSC、XRD 和 TEM 分析对其进行了评估。使用体外 BBB 模型的 BBB（血脑屏障）通道研究表明，CS-TNPs 能够有效地穿过 BBB。与纯 TMZ 相比，细胞活力测定数据表明 CS-TNP 的细胞毒性更高。U87 MG 细胞中的 CD44 受体阻断试验和受体中毒试验证实了 CD44 受体和内吞作用介导的（凹窝途径）摄取 CS-TNP。CS-TNPs 能够在 U87 MG 细胞中产生 ROS。在 Wistar 大鼠中进行体内药代动力学和生物分布研究。体内结果显示，与单独使用 TMZ 相比，CS-TNP 的药代动力学特征显着增强。生物分布结果表明，与证实纳米粒子脑靶向能力的纯药物相比，CS-TNPs 在脑中积累更高的 TMZ。从所有获得的结果可以得出结论，CS-TNPs 是很有前途的载体，可以将 TMZ 输送到大脑，用于脑肿瘤的靶向治疗。生物分布结果表明，与证实纳米粒子脑靶向能力的纯药物相比，CS-TNPs 在脑中积累更高的 TMZ。从所有获得的结果可以得出结论，CS-TNPs 是很有前途的载体，可以将 TMZ 输送到大脑，用于脑肿瘤的靶向治疗。生物分布结果表明，与证实纳米粒子脑靶向能力的纯药物相比，CS-TNPs 在脑中积累更高的 TMZ。从所有获得的结果可以得出结论，CS-TNPs 是很有前途的载体，可以将 TMZ 输送到大脑，用于脑肿瘤的靶向治疗。