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Biodegradable copolymers with identical cationic segments and their performance in siRNA delivery

Ruogu Qi, Shi Liu, Jie Chen, Haihua Xiao, Lesan Yan, Yubin Huang, Xiabin Jing
Journal of Controlled Release 2012 April 30, 159 (2): 251-60
The biodegradable cationic copolymers monomethoxy poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine) (mPEG-b-PCL-b-PLL, further abbr. as "M") with a PCL block of different lengths and with a triazole linkage between the PCL and PLL blocks were synthesized via ring-opening polymerization of ε-caprolactone and L-lysine N-carboxyanhydride and click reactions. With the copolymer without the PCL block (mPEG-b-PLL, further abbr. as "P") as a control, self-assembling and complexation of these copolymers with siRNA were studied. siRNA-loading capacity, siRNA delivery performance and cellular uptake of the complexation products, namely complex from P (P-complex) and complexes from M1 and M2 (M1-complex and M2-complex), were further examined and correlated to their block-copolymer compositions. The results showed the block copolymers P, M1 and M2 have strong enough binding ability so that the complexes formed can resist the heparin displacement and RNase degradation. Compared to P-complex, M-complexes have smaller size and higher particle density so that they can be internalized via endocytosis more easily than free siRNA or P-complex and they display higher siRNA delivery efficiency and higher gene silencing efficiency than P-complex. The silencing efficiency of micellar complex is close to that of Lipofectamine(TM) 2000 and much better than PEI-25kDa. Therefore, mPEG-b-PCL-b-PLL is expected to be a promising siRNA carrier.


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