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آکتا بیومتریال
جزئیات رویداد
همایش ، رویداد ، ژورنال
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  • specific effects of pegylation on gene delivery efficacy of polyethylenimine: interplay between peg substitution and n/p ratio

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    • تاریخ ارائه: 1392/01/01
    • تاریخ انتشار در تی پی بین: 1392/01/01
    • تعداد بازدید: 648
    • تعداد پرسش و پاسخ ها: 0
    • شماره تماس دبیرخانه رویداد: -
     while an effective non-viral gene carrier, 25 kda branched polyethylenimine (pei) is cytotoxic, and decreasing its toxicity while maintaining its functionality is vital. conjugation of carriers with polyethylene glycol (peg) is a common approach to decreasing toxicity and improving biodistribution; however, the effect of pegylation on pei transfection efficacy is contradictory at present. the aim of this work was to reveal the details of this dependence. polymers were synthesized by grafting 2 kda peg to 25 kda pei at multiple ratios. unlike typical investigations, parallel studies based on either total polymer weight or pei-backbone weight were employed at the same time for accurate investigation into the specific effects of pegylation. polymers were assessed for toxicity and plasmid dna (pdna) binding, while polyplexes were formed at various polymer/pdna weight ratios and monitored by dynamic light scattering (dls) in the presence of serum. the efficacy of the polyplexes for pdna delivery and transgene expression in hek293 cells was assessed by flow cytometry. this approach unexpectedly revealed that increased peg substitution caused lower toxicity and pdna-binding on a per total polymer weight basis, but not on a per pei-backbone weight basis. dls indicated that high pegylation prevents an increase in polyplex size in the presence of serum. plasmid uptake and transgene expression were found to have a complex relationship with peg substitution, dependent on the polymer/plasmid-dna weight ratio. pegylation generally decreased the transfection efficacy of pei, but under ideal conditions of peg substitution and polymer/pdna ratio, pegylation provided more effective carrier formulations than the native pei itself.

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