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  • Title: A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study.
    Author: Lai Y, Long Y, Lei Y, Deng X, He B, Sheng M, Li M, Gu Z.
    Journal: J Drug Target; 2012 Apr; 20(3):246-54. PubMed ID: 22118403.
    Abstract:
    In this paper, a novel micelle for anti-tumor drug delivery was reported. Two 7-carboxymethoxy coumarin molecules were immobilized on the terminal group of a methoxy poly(ethylene glycol) chain via l-lysine as linker. The amphiphilic 7-carboxymethoxy coumarin monoend-functionalized methoxy poly(ethylene glycol) (mPEG-Lys-DCOU) chains were self-assembled micelles. Anti-tumor drug doxorubicin was loaded in the mPEG-Lys-DCOU micelles and the release profile was studied. The cytotoxicity of mPEG-Lys-DCOU was evaluated by NIH 3T3 fibroblasts. The drug-loaded micelles were incubated with HepG2 tumor cells to investigate the in vitro anti-tumor effect. The in vivo inhibition efficacy of drug-loaded micelles was carried out on 4T1 breast cancer animal model. The results showed that both hydrophobic and π-π stacking interactions within mPEG-Lys-DCOU amphiphiles were contributed to the self-assembly. Both blank and drug loaded micelles were monodisperse nanoparticles with the average diameters around 300 nm. The release profile exhibited certain pH dependence. The drug release rate at pH = 5.5 was much faster than that at pH = 7.4. mPEG-Lys-DCOU amphiphiles were non-toxic to NIH 3T3 fibroblasts. Both in vitro and in vivo studies demonstrated that the inhibition efficacy of drug-loaded micelles were comparable to that of doxorubicin hydrochloride. mPEG-Lys-DCOU micelles are promising carriers for anti-tumor drug delivery.
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