Chondroitin sulfate conjugation facilitates tumor cell internalization of albumin nanoparticles for brain-targeted delivery of temozolomide via CD44 receptor-mediated targeting

Abstract

In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated bydesolvation 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 thepure 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. Graphical abstract.