Synthesis, functionalization and evaluation of dendrimers, based on melamine as possible systems for drug delivery

Possible systems for drug delivery made from dendrimers based on melamine were synthesized. Convergently synthesized dendrons 1 and 2 were decorated with pyridyldisulfide and tetraethylene glycol groups for reactivity towards thiol-containing compounds and increased water-solubility, respectively. Dendron 1 can be easily functionalized with small molecule thiol-containing drugs such as captopril, an antihypertensive drug. While dendron 2 is found to be non-immunogenic in test rabbits, its conjugate with an antigenic peptide from an enterotoxigenic E. coli, 6, is. Dendrimer 15 is a third generation dendrimer synthesized on moderate scale by an accelerated approach, and is decorated with orthogonally protected amino groups in the periphery. Post-synthetic manipulation of 15 gives 18, which is a 57-KDa PEGylated system that is also reactive towards thiol-containing compounds. This dendrimer is a potential system that can exhibit enhanced permeability and retention (EPR) in tumors as an anticancer drug delivery system. All intermediates and products can be characterized by NMR spectroscopy and mass spectrometry.