Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery

Polycations as one of non-viral vectors have gained increasing attentions. In this paper, polyethylenimine(PEI)-grafted polycarbonates (PMAC-g-PEIx) were synthesized as a kind of biodegradable polycations for gene delivery. Backbone polymer, poly(5-methyl-5-allyloxycarbonyl-trimethylene carbonate) (PMAC) was synthesized in bulk catalyzed by immobilized porcine pancreas lipase (IPPL). Then, PMAC-O, the allyl epoxidation product of PMAC, was further modified by PEIx with low molecular weight (x = 423, 800 and 1800). The MWs of PMAC-g-PEIx, measured by GPC-MALLS, were 81,900, 17,9900 and 200,60 g/mol with polydispersities of 1.2, 1.4 and 1.7, respectively. PMAC-g-PEIx/DNA polyplexes had similar buffer capabilities. In vitro experiments demonstrated that the PAMC-g-PEIx showed much low cytotoxicity and enhanced transfection efficiency could be found in comparison with PE125K in 293T cells. Furthermore, pre-incubation of PMAC-g-PE11800 showed a weakening binding capacity with DNA. The biodegradability of PMAC-g-PEIx can facilitate the efficient release of pDNA from polyplexes and reduce cell cytotoxicity. These results suggested that PMAC-g-PEIx would be a promising non-viral biodegradable vector for gene delivery system. (C) 2009 Elsevier Ltd. All rights reserved.