A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study

• Published in: Journal of drug targeting 2012-04, Vol.20 (3), p.246-254
• Main Authors: Lai, Yusi, Long, Youyu, Lei, Ying, Deng, Xin, He, Bin, Sheng, Mingming, Li, Ming, Gu, Zhongwei
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Coumarins - adverse effects; Coumarins - chemistry; doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug Carriers - therapeutic use; Drug Compounding; Drug delivery; Female; General pharmacology; Hep G2 Cells; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; micelle; Micelles; mPEG-Lys-DCOU; Nanoparticles - adverse effects; Nanoparticles - chemistry; Nanoparticles - ultrastructure; NIH 3T3 Cells; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - adverse effects; Polyethylene Glycols - chemistry; Random Allocation; Specific Pathogen-Free Organisms; π-π stacking
• ISSN: 1061-186X; 1029-2330
• DOI: 10.3109/1061186X.2011.639023

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.