SYNTHESIS AND CHARACTERIZATION OF LIGAND ANCHORED POLY PROPYLENEIMINEDENDRIMERS FOR THE TREATMENT OF BRAIN GLIOMA

Parashar Ashish Kumar*, Singh Gurdeep

Oriental College of Pharmacy and Research, Oriental University, Indore, Madhya Pradesh

ABSTRACT

The goal of this study was to develop and characterize Angiopep-2 attached PEGylated Polypropylene imine (PPI) dendrimers for Temozolomide administration to brain gliomas. For surface neutralisation, synthesized PPI dendrimers were conjugated with PEG-2000. PEGylated PPI dendrimers were further coupled with Angiopep-2 (ANG-PEG-PPP) for enhanced medication transport across the blood-brain barrier (BBB) into the area of the brain tumour. Temozolomide loaded ligand-conjugated PPI dendrimers (TAPP) were characterized for size, % drug loading, cumulative drug release, and cell line studies. The drug loading was found to be 57.42±0.8%. In vitro release profile exhibited an early burst release followed by zero-order kinetics (46.8±0.8% in 24 hours). TAPP dendrimers showed improved antiproliferative efficacy against C6 glioma cells in MTT assays and cellular uptake investigations. The ability of TAPP to target cancer cells was examined using an in vitro co-culture model of BCECs and C6 glioma cells. Our findings suggest that Angiopep-2 coupled PEGylated PPI dendrimers could be a suitable nanocarrier for Temozolomide delivery to brain gliomas.

Keywords:

Dendrimer, Polyethylene glycol, Temozolomide, angiopep-2, drug targeting, glioblastoma multiforme