An Innovative in Situ Method of Creating Hybrid Dendrimer Nano-assembly: An Efficient Next Generation Dendritic Platform for Drug Delivery

Dendrimers have proven to be effective for drug delivery and their biodisposition varies with change on their surface, generation and core. In an effort to understand the role of critical nanoscale design parameters, we developed a novel hybrid dendrimer approach to harness unique features of individual dendrimers and create a nano-assembly. We report an easy in situ method of creating hybrid dendrimer nano-assembly by mixing G4.0 PAMAM (-NH) and G3.5 PAMAM (-COONa) dendrimers with a chemotherapeutic drug docetaxel (DTX). Zeta potential, HR-TEM, H-NMR proved the formation of nano-assembly. In vitro dissolution, release studies revealed pH dependent dissolution and sustained drug release. Cellular uptake, cytotoxicity, and flow cytometric analysis in human/mouse glioblastoma cells indicated the effectiveness of hybrid dendrimers. The oral administration of the hybrid dendrimers showed pharmacokinetic equivalence to intravenous injection of commercially available Taxotere®. Hybrid dendrimer concept provides much needed fine-tuning to create multistage next-generation dendritic platform in nanomedicine.