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

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.

• Authors: Yusi Lai, Youyu Long, Ying Lei, Xin Deng, Bin He, Mingming Sheng, Ming Li, Zhongwei Gu
• Journal: Journal of drug targeting (J Drug Target) Vol. 20 Issue 3 Pg. 246-54 (Apr 2012) ISSN: 1029-2330 [Electronic] England
• PMID: 22118403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Coumarins
• Drug Carriers
• Micelles
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacology, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Coumarins (adverse effects, chemistry)
• Doxorubicin (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Drug Carriers (administration & dosage, chemistry, pharmacology, therapeutic use)
• Drug Compounding
• Female
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Micelles
• NIH 3T3 Cells
• Nanoparticles (adverse effects, chemistry, ultrastructure)
• Polyethylene Glycols (adverse effects, chemistry)
• Random Allocation
• Specific Pathogen-Free Organisms