Design, synthesis and in vitro evaluation of a novel 'stealth' polymeric gene vector
| Autor: | He Guosen, Luo Xin, Subbu S. Venkatraman, Feng Min |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
biology
Polymers Stereochemistry Polyesters Genetic Vectors technology industry and agriculture Cationic polymerization Pharmaceutical Science Transfection biology.organism_classification In vitro Polyethylene Glycols HeLa chemistry.chemical_compound chemistry PEG ratio Biophysics Humans Polyethyleneimine MTT assay Lactic Acid Cytotoxicity Ethylene glycol HeLa Cells |
| Zdroj: | International Journal of Pharmaceutics. 350:344-350 |
| ISSN: | 0378-5173 |
| Popis: | We report on the synthesis of a novel gene carrier that has low interaction with serum components, as well as low cytotoxicity. Cationic copolymers composing branched poly(ethylenimine) (PEI) grafted with hydrophilic poly(ethylene glycol) (PEG) and poly(l-lactic acid) (PLLA) or small-molecule oleoyl were synthesized and evaluated as novel gene carriers in this study. The copolymers were complexed with plasmid DNA and the resulting polyplexes were approximately 140nm in diameter and had a positive surface potential (zeta=+13.8mV) at the N/P ratio of 10/1. The experiments showed that copolymers with the oleoyl moiety were superior to the other two copolymers (with PLLA), in terms of in vitro gene transfection efficiency. Safety studies using MTT assay indicated much lower cytotoxicity of the oleoyl polyplexes than the pDNA/PEI complexes. The intracellular behavior of the polyplexes was monitored by confocal laser scanning microscopy, and it was found that the polyplexes were internalized into HeLa cells very effectively. At the same time, the plasmid DNA carried by the oleoyl-containing copolymers was found to localize in the nucleus of the recipient cells. One experiment comparing serum-free and serum-containing media indicated that the oleoyl polyplexes may be able to evade the reticulo-endothelial system (RES) better than the PEI-pDNA complex. |
| Databáze: | OpenAIRE |
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