Fabrication of novel coumarin derivative functionalized polypseudorotaxane micelles for drug delivery.

PMID 23235914


The fabrication and drug delivery of novel polypseudorotaxane micelles with small molecule coumarin derivative as hydrophobic segment were reported. 7-Carboxymethoxy coumarin was immobilized on the terminal hydroxyl groups of poly(ethylene glycol) (PEG). The modified PEG chains were threaded in α-cyclodextrins (α-CDs) to form polypseudorotaxanes. The polypseudorotaxanes self-assembled into supramolecular micelles driven by hydrophobic interaction and polypseudorotaxane crystallization. Anti-tumor drug doxorubicin (DOX) was trapped in the micelles. The structure, morphology, drug release profile and cytotoxicity of the micelles were investigated. The in vitro anti-tumor studies including cellular uptake and inhibition efficiency were performed on mice cancer cell lines of TC1 lung cancer cells and B16 melanoma cells. The results revealed that the 7-carboxymethoxy coumarin modified PEG could thread into the cavity of α-CDs to form necklace-like polypseudorotaxanes. The polypseudorotaxanes self-assembled into spherical micelles with the mean size of 30 nanometers, and the size was increased to about 80 nanometers after the drug was loaded. The drug loading content of the micelles was decreased with increasing the chain length of PEG. The sustaining release of DOX could last for 32 hours. The polypseudorotaxane micelles were non-toxic to both TC1 and B16 cells. The IC50 of the DOX loaded polypseudorotaxane micelles with PEG2k was lower than that of micelles with PEG4k or PEG6k both in TC1 and B16 cells.