Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positive charged amino acids

Dendrimers are nanostructured “architectural motifs” with a well tailored polymeric structure, symmetric tree-like shape, the presence of several functional groups and inner cavities, and are of eminent interest in many biomedical applications as drug delivery, gene transfection and imaging. In this paper, reliable protocols for the synthesis of polyester-based, hydrolysable, amphiphilic polycationic dendrimers were developed. A C-18 hydrocarbon chain provided by a biocompatible fatty acid as stearic acid and second and third generation dendrons based on 2,2-bis(hydroxymethyl)propionic acid were built on 2,2-bis(hydroxymethyl)propanol and pentaerythritol as core molecules. αN-BOC-ω’N-(NO2)-L-arginine alone, mixed with αN,εN-di-BOC-L-lysine or also with N,N’-dimethylglycine and αN-BOC-methylglycine were successfully bound to the prepared polyester neutral scaffolds and after the removal of protecting groups, five cationic dendrimers were obtained. Their structure was confirmed by NMR analysis and experimental molecular weight. Their buffer capacity, comparable to that of PEIs, was optimal, high viability percentage values were obtained from cytotoxicity essays and zeta potential and mean particles size were in the desired range. The synthesized nanostructured compounds that harmonize a multifunctional polycationic shell, a biodegradable uncharged polyester matrix and a C-18 hydrophobic portion helpful for an improved Hydrophilic-Lipophilic Balance in their structure, embody all the fundamental features to be suitable for biomedical applications.