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TY - JOUR AU - Thomas, Mini AU - Ge, Qing AU - Lu, James J. AU - Chen, Jianzhu AU - Klibanov, Alexander PY - 2005 DA - 2005/03/01 TI - Cross-linked Small Polyethylenimines: While Still Nontoxic, Deliver DNA Efficiently to Mammalian Cells in Vitro and in Vivo JO - Pharmaceutical Research SP - 373 EP - 380 VL - 22 IS - 3 AB - Polyethylenimine (PEI) is among the most efficient nonviral gene delivery vectors. Its efficiency and cytotoxicity depend on molecular weight, with the 25-kDa PEI being most efficient but cytotoxic. Smaller PEIs are noncytotoxic but less efficient. Enhancement in gene delivery efficiency with minimal cytotoxicity by cross-linking of small PEIs via potentially biodegradable linkages was explored herein. The hypothesis was that cross-linking would raise the polycation’s effective molecular weight and hence the transfection efficiency, while biodegradable linkages would undergo the intracellular breakdown after DNA delivery and hence not lead to cytotoxicity. Toward this goal, we carried out cross-linking of branched 2-kDa PEI and its 1:1 (w/w) mixture with a linear 423-Da PEI via ester- and/or amide-bearing linkages; the in vitro and in vivo gene delivery efficiency, as well as toxicity to mammalian cells, of the resultant cross-linked polycations were investigated. SN - 1573-904X UR - https://doi.org/10.1007/s11095-004-1874-y DO - 10.1007/s11095-004-1874-y ID - Thomas2005 ER -