Peptide Dendrimer Functionalized with Amphiphilic Triblock Copolymers: Synthesis and Characterization

Abstract

Poly(l‐lysine) dendrimer end‐functionalized with arginine‐6‐oligomer conjugated biodegradable poly(3‐hydroxybutyrate) (PHB)–poly(ethylene glycol) (PEG)–PHB copolymer may be considered a promising macromolecular drug delivery vehicle. To prepare amphiphilic triblock copolymers, bulk ring‐opening polymerization (ROP) of (R,S)‐β‐butyrolactone initiated with poly(ethylene glycol) is carried out. The copolymers are synthesized with a high yield of 90%. The structure and physical–chemical properties of the obtained products are confirmed by hydrogen and carbon nuclear magnetic resonance (1H and 13C NMR), viscosity method, gel permeation chromatography (GPC), matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF), and differential scanning calorimetry (DSC) technique. Furthermore, the cytotoxicity of the synthesized copolymers is evaluated with a bacterial luminescence test and protozoan assay, which show that the obtained copolymers are not cytotoxic. Poly(l‐lysine) dendrimer end‐functionalized with arginine‐6‐oligomer is further covalently bonded to a copolymer using the 1,1'‐carbonyldiimidazole/4‐(dimethylamino)pyridine (CDI/DMAP) coupling method. The presence of a newly formed urethane bond between the peptide dendrimer and the copolymer is confirmed by 1H NMR studies. This novel peptide dendrimer functionalized with an amphiphilic triblock copolymer can be applied as a compatible biodegradable material for drug carrier applications.β‐butyrolactone; biodegradable polymers; drug delivery system; peptide dendrimers; ring‐opening polymerization image