期刊
JOURNAL OF CONTROLLED RELEASE
卷 103, 期 1, 页码 221-233出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2004.11.011
关键词
biodegradable; gene delivery; PEG copolymers; Nonviral; DNA dosage
Biodegradable cationic polymers have become promising alternatives to traditional polycationic gene delivery systems in which the high charge densities of high molecular weight polymers contribute significantly to cellular toxicities. Previous research has shown that biodegradable, multiblock copolymers (MBC), PEG-PLL-g-16% His, are efficient gene carriers with negligible cellular toxicities. The present research was designed to characterize the polymer degradation as well as to determine the biodistribution of the MBC after systemic administration. Polymer degradation was performed in buffer as a function of pH, in serum and within polymer/pDNA complexes. The MBC exhibited exponential decay with a half-life (t(1/2)) of similar to 14 min at pH 9.0, similar to 5 h at pH 7.4 and similar to 2 h in serum. However, there was little or no degradation observed at pH 4.0 and the MBC within the complexes degraded between 4 and 8 h in serum. Biodistribution data performed with fluorescently labeled polymer and pDNA revealed that intact complexes remained in the blood up to 3 days, which was also reflected in the organs as a function of time. Therefore, the cumulative data suggest that PEG may be sterically stabilizing complexes in vivo via dysopsonization in which serum proteins mask the complexes from elements of the reticuloendothelial system (RES). (c) 2004 Elsevier B.V. All rights reserved.
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