New self-assembling polyaspartylhydrazide copolymer micelles for anticancer drug delivery

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C-16) moieties on polymer backbone, and the structure of obtained PAHy-PEC2000-C-16 copolymer have been characterized by 2D H-1/C-13 NMR experiments PAHy-PEC2000-C-16 copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D H-1 NMR NOESY experiments The presence of cross-peaks for protons of C-16 and PAHy portions, Indicated that the two domains are in close proximity forming micelle core The critical aggregation concentration (CAC) values of PAHy-PEG(2000)-C-16 amphiphilic graft copolymer was determined in water by fluorescence technique, and it was demonstrated that PAHy-PEG(2000)-C-16 micelles are well suited to be micellar vehicle of highly hydrophobic molecules Therefore, anticancer drug tamoxifen, used as a model hydrophobic molecule, was loaded into PAHy-PEG(2000)-C-16 micelles obtaining an increase of drug solubility of about 3000 times Transmission electron microscopy (TEM) observations showed the spherical morphology of micelles formed by PAHy-PEG(2000)-C-16 copolymer with a mean diameter of about 30 nm, as confirmed also by dynamic light scattering (DLS) studies. Finally, in vitro cell viability studies were carried out on human breast cancer cells (MCF-7) testing the pharmacological activity of tamoxifen-loaded PAHy-PEC2000-C-16 micelles. in comparison with free tamoxifen at different drug concentrations, demonstrating that tamoxifen-loaded PAHy-PEG(2000)-C-16 micelles exhibited a concentration-dependent cytotoxic activity (C) 2010 Elsevier B.V. All rights reserved.