Synthesis and characterization of Agiopep-2 anchored PEGylated poly propyleneimine dendrimers for targeted drug delivery to glioblastoma multiforme
Abstract
The present study was aimed at developing and exploring the use of Angiopep-2 anchored PEGylated Poly propyleneimine (PPI) dendrimers for targeted delivery of paclitaxel to the brain glioma. PPI dendrimers were synthesized and modified with PEG-2000 for surface neutralization. PEGylated PPI dendrimers were further conjugated with Angiopep-2 (ANG-PEG-PPP) for improved drug delivery across blood brain barrier (BBB) into the vicinity of brain glioma. Ligand conjugated PPI dendrimers were loaded with Paclitaxel (PAPP) and characterized for size, percentage drug loading, cumulative drug release and cell line studies. Drug loading was found to be 57.42±0.8% while in vitro release profile depicted an initial burst release followed by zero order kinetics (46.8±0.8% in 24hr). MTT assay and cellular uptake studies on PAPP dendrimers demonstrated an enhanced antiproliferative activity against C6 glioma cells. Targeting potential of PAPP was evaluated using in vitro co culture model of BCECs and C6 glioma cells. Our study concludes, Angiopep-2 conjugated PEGylated PPI dendrimers as a promising nanocarrier for targeted delivery of paclitaxel to the brain glioma.
Keywords: Dendrimer, Polyethylene glycol, paclitaxel, angiopep-2, drug targeting, glioblastoma multiforme
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