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  • Title: Polyethylenimine with acid-labile linkages as a biodegradable gene carrier.
    Author: Kim YH, Park JH, Lee M, Kim YH, Park TG, Kim SW.
    Journal: J Control Release; 2005 Mar 02; 103(1):209-19. PubMed ID: 15710512.
    Abstract:
    Polyethylenimine (PEI) is a gene carrier with high transfection efficiency. However, PEI has high cytotoxicity, which depends on its molecular weight. To reduce the cytotoxicity, degradable PEIs with acid-labile imine linkers were synthesized with low molecular weight PEI1.8K (1.8 kDa) and glutadialdehyde. The molecular weights of the synthesized acid-labile PEIs were 23.7 and 13 kDa, respectively. The half-life of the acid-labile PEI was 1.1 h at pH 4.5 and 118 h at pH 7.4, suggesting that the acid-labile PEI may be rapidly degraded into nontoxic low molecular weight PEI in acidic endosome. In a gel retardation assay, plasmid DNA (pDNA) was completely retarded at a 3:1 N/P (nitrogen of polymer/phosphate of DNA) ratio. The zeta potential of the polyplexes was in the range of 46.1 to 50.9 mV and the particle size was in the range of 131.8 to 164.6 nm. In vitro transfection assay showed that the transfection efficiency of the acid-labile PEIs was comparable to that of PEI25K. In toxicity assay, the acid-labile PEI was much less toxic than PEI25K, due to the degradation of acid-labile linkage. Therefore, the acid-labile PEIs may be useful for the development of a nontoxic polymeric gene carrier.
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