Self-Catalyzed Degradable Cationic Polymer for Release of DNA

The controlled release of siRNA or DNA complexes from cationic polymers is an important parameter design in polymer based delivery carriers:, In this work, We use the self catalyzed degradable poly(2-dimethylaminoethyl acrylate) (PDMAEA) to strongly bind, protect, and then release oligo DNA (a mimic for siRNA) without the need for a cellular or external trigger. This self-catalyzed hydrolysis process of PDMAEA forms poly(acrylic acid) and N,N'-dimethylamino ethyl ethanol, both of which have little or no toxicity to cells, and tissues. We found that PDMAEA makes an ideal component of a delivery carrier by protect in the oligo DNA for a sufficiently long period of time of transfect most cells (80% transfection after 4 h) and then has the capacity to release the DNA inside the cells after similar to 10 h. The PDMAEA formed large nanoparticle complexes with oligo DNA of similar to 400 nm that protected the oligo DNA from DNase in serum. The nanoparticle complexes showed to toxicity for all molecular weights at a nitrogen/phosphorus (N/P) ratio of 10. Only the higher molecular weight polymers at very high N/P ratios of 200 showed significant levels of cytotoxicity. These attributes make PDMAEA a promising candidate as a component in the design of a gene delivery carrier without the concern about accumulated toxicity of nanoparticles in the human body after multi-administration, an issue that has become increasingly more important.