Synthesis and evaluation of PEG derivatized nanostructures as potential delivery carrier for hydrophobic drugs

Abstract

Dendrimers are three-dimensional, monodispersed polymers with diverse biological properties. In this study, a novel dendritic nanostructure was synthesized using trimesic acid (TMA) as the core molecule and poly(ethylene glycol) (PEG₂₀₀₀) as the branching units. The coupling of PEG₂₀₀₀ with TMA was achieved through the formation of ester bonds between the carboxylic groups of TMA and the hydroxyl groups of PEG. The successful formation of the dendritic nanostructure was confirmed using FTIR and proton NMR spectroscopy. The encapsulation of the poorly water-soluble anticancer drug paclitaxel (PTX) into the dendritic nanostructure was also validated through FTIR and ¹HNMR analysis. The PTX-loaded TMA-PEG nanostructure was further characterized using DLS, TEM, DSC, and XRD techniques. In vitro drug release studies in different physiological buffers demonstrated the release profile of PTX from the nanostructures. Haemolytic toxicity studies revealed that both blank dendritic structures and PTX-loaded formulations exhibited no toxicity toward human red blood cells, indicating excellent biocompatibility. Furthermore, in vitro cell viability assays against A549 (human lung cancer) and MCF7 (human breast cancer) cell lines showed dose- and time-dependent cytotoxic effects. Importantly, the PTX-loaded TMA-PEG nanostructure demonstrated significantly higher cytotoxicity compared to free PTX. Thus, the developed dendritic nanostructure shows promise as an efficient drug delivery system for hydrophobic anticancer drugs like paclitaxel, offering improved efficacy and biocompatibility.