Design and Synthesis of Amphiphilic Graft Polyphosphazene Micelles for Docetaxel Delivery

The structural versatility of polydichlorophosphazene derived from the inestimable possibilities to functionalize the two halogens, attached to each phosphazene main chain unit, attracted increasing attention in the last decade. This uncountable chemical derivatization is doubled by the amphiphilic roleplay demonstrated by polyphosphazenes containing twofold side-chained hydrophilic and hydrophobic moieties. Thus, it is able to encapsulate specific bioactive molecules for various targeted nanomedicine applications. A new amphiphilic graft, polyphosphazenes (PPP/PEG-NH/Hys/MAB), was synthesized via the thermal ring-opening polymerization of hexachlorocyclotriphosphazene, followed by a subsequent two-step substitution reaction of chlorine atoms with hydrophilic methoxypolyethylene glycol amine/histamine dihydrochloride adduct (PEG-NH2)/(Hys) and hydrophobic methyl-p-aminobenzoate (MAB), respectively. Fourier transform infrared spectroscopy (FTIR) and H-1 and P-31-nuclear magnetic resonance spectroscopy (NMR) have been used to validate the expected architectural assembly of the copolymer. Docetaxel loaded micelles based on synthesized PPP/PEG-NH/Hys/MAB were designed by dialysis method. The micelles size was evaluated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug release profiles from the PPP/PEG-NH/Hys/MAB micelles were established. In vitro cytotoxicity tests of PPP/PEG-NH/Hys/MAB micelles loaded with Docetaxel revealed that designed polymeric micelles exhibited an increased cytotoxic effect on MCF-7 cells.

Automated summary

The structural versatility of polydichlorophosphazene, due to the ability to functionalize the halogens attached to each phosphazene main chain unit, has gained attention in recent years. Polyphosphazenes with dual hydrophilic and hydrophobic side-chains have shown potential for targeted nanomedicine applications. A new amphiphilic graft, PPP/PEG-NH/Hys/MAB, was synthesized and validated using spectroscopic techniques. Drug-loaded micelles based on PPP/PEG-NH/Hys/MAB exhibited increased cytotoxicity on MCF-7 cells.