Abstract：
:High-molecular-weight polyethylenimine (25 kDa, PEI25k) is one of the most common cationic polymers utilized in non-viral gene therapy. However, its methylene backbone (-CH(2)CH(2)N(x)-) and high charge density can result in poor biodegradability and high toxicity to cells. We hypothesize that optimizing the polymer length and charge density of PEI analogues may result in decreased toxicity and higher transfection efficiency, and improved biocompatibility in vivo. A series of PEI analogues with controlled molecular weight and charge density were synthesized by grafting low-molecular-weight PEI800 (800 Da) to a polyaspartate peptide backbone of varying degrees of polymerization. The optimum polymer had a degree of polymerization of 65 with an average of 16 PEI800 groups conjugated to it. All of the polycations investigated in the study caused inflammation and apoptosis/necrosis in the liver and spleen of rodents 24h post-injection; however, by day 5, the optimized poly(aspartate-g-PEI800) polymer and PEI800 did not show tissue damage or apoptosis, whereas PEI25k exhibited evidence of apoptosis/necrosis in the kidneys and spleen. Our study points to the need to optimize gene carriers to minimize toxicity, especially important for the safe delivery of therapeutic genes to explicit organs.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Xiong MP,Forrest ML,Ton G,Zhao A,Davies NM,Kwon GSdoi
10.1016/j.biomaterials.2007.07.043subject
Has Abstractpub_date
2007-11-01 00:00:00pages
4889-900issue
32eissn
0142-9612issn
1878-5905pii
S0142-9612(07)00557-1journal_volume
28pub_type
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