10. Biodegradable Polymers for gene / nucleic acid Delivery SUNBRIGHT® ME-DT & DT series

NOF has provided new biodegradable polymers for gene/nucleic acid delivery, SUNBRIGHT® ME-DT and DT series. The poly cationic block polymer, PEG-PAsp(DET) (polyethylene glycol-b-poly{N’-[N-(2-aminoethyl)-2-aminoethyl] aspartamide}), and homo polymer, PAsp(DET) forming polymeric micelles with poly anions such as gene/nucleic acid (ex. plasmid DNA and mRNA) enable efficient delivery of gene/nucleic acid with a low toxicity compared toconventional cationic carriers.


Figure.1 Formation of polymer micelles through the electrostatic interaction between SUNBRIGHT® ME-DT (PEG-PAsp(DET) Block) / SUNBRIGHT® DT (PAsp(DET) Homo polymer) and plasmid DNA.


Figure.2 Protonation behavior and membrane disruption activity of SUNBRIGHT® ME-DT series (PEG-PAsp (DET) Block,).


Figure.3 Protonation behavior and membrane disruption activity of SUNBRIGHT® ME-DT series (PEG-PAsp (DET) Block,) K. Miyata et al. J. Am. Chem. Soc. 130 :16287-16294 (2008)

SUNBRIGHT® ME-DT, DT series having characteristic protonation behavior responing to endo-somal pH condition achieve selective disruption of endosomal membranes, follo-wed by efficient delivery of plasmid DNA and mRNA etc.

K. Miyata et al. J. Am. Chem. Soc. 130 :16287-16294 (2008)


Low accumulative toxicity by viodegradability

Figure.4 Biodegradability evaluation of SUNBRIGHT® ME-DTseries(PEG-PAsp(DET) Block polymer) in physiological buffer (pH7.4, 150mM NaCl).

Remarkable low toxicity by the biodegradability

Figure.5 Toxicity evaluation of SUNBRIGHT® DTseries (PAsp(DET) Homo polymer) using Human Umbilical Vein Endothelial Cells (HUVEC). (Number of day means period for pre-incubation of polymers inphysiological buffer.)

SUNBRIGHT® ME-DT and DT series having biodegradability in physiological condition shows a lower toxicity comparedwith conventional cationic polymer for nucleic acid delivery such as polyethyleneimine (PEI:-(CH2CH2NH)n-). Moreover,the toxicity decreases apparently in a time-dependence manner comparing to the PGlu(DET) (DET-derivative polymer of Poly(Glutamic acid)) having no remarkable biodegradability in physiological condition.


Examples of use for SUNBRIGHT® ME-DT and DT series >>

(PAsp(DET), homo polymer) (DP of PAsp(DET)=ca. 50 )

PEG-PAsp(DET), block polymer MW of PEG=ca. 12,000, DP of PAsp(DET)=ca. 70