Amphiphilic Methoxy Poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-dimethylaminoethyl methacrylate) Cationic Copolymer Nanoparticles as a Vector for Gene and Drug Delivery

• Published in: Biomacromolecules 2010-09, Vol.11 (9), p.2306-2312
• Main Authors: Yue, Xinye, Qiao, Yong, Qiao, Ning, Guo, Shutao, Xing, Jinfeng, Deng, Liandong, Xu, Jianqing, Dong, Anjie
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Applied sciences; Biological and medical sciences; Cations; Cell Survival - drug effects; Cells, Cultured; DNA - administration & dosage; DNA - genetics; DNA - metabolism; Drug Carriers; Drug Delivery Systems; Drug Synergism; Electrophoretic Mobility Shift Assay; Exact sciences and technology; General pharmacology; Humans; Kidney - cytology; Kidney - drug effects; Medical sciences; Nanoparticles; Organic polymers; Paclitaxel - pharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polymers - administration & dosage; Polymers - chemical synthesis; Polymers - chemistry; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Quaternary Ammonium Compounds - administration & dosage; Quaternary Ammonium Compounds - chemical synthesis; Quaternary Ammonium Compounds - chemistry
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm100410m

We studied methoxy poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-dimethylaminoethyl methacrylate) (mPEG-b-PCL-b-PDMAEMA) nanoparticles as the codelivery vector of hydrophobic drug and pDNA by employing dynamic light scattering (DLS), ζ potential, transmission electron microscopy (TEM), gel retardation assay, and confocal microscopy, and subsequently its in vitro cytotoxicity and transfection efficiency were tested. mPEG-b-PCL-b-PDMAEMA nanoparticles (NPs) with or without paclitaxel are both able to complex with pDNA completely when N/P ratio is equal to or above 3, and the combinatorial deliveries of paclitaxel and pDNA have equivalent transfection efficiency compared to blank NPs/pDNA complexes when N/P ratio is equal to or above 15, which indicates that the payload of hydrophobic drug does not influence pDNA condensation and transfection efficiency. Importantly, the in vitro cell experiment results confirm that the introduction of hydrophobic segment between mPEG and PDMAEMA segments can largely improve the gene transfection efficiency, which is about 15 times that of mPEG-b-PDMAEMA. NPs/pDNA complexes can be efficiently internalized into 293T cells after transfection for 2 h. The drug release rate of paclitaxel-loaded NPs in pH 5.0 release medium is higher than that in pH 7.2 release medium. These results suggest that mPEG-b-PCL-b-PDMAEMA NPs may be a promising vector to deliver anticancer drugs and pDNA simultaneously for achieving the synergistic/combined effect on cancer therapies.