Synthesis and characterization of polycation block copolymer Poly(L-lysine)-b-poly[N-(N′,N′-diisopropyl-aminoethyl)aspartamide] as potential pH responsive gene delivery system

A series of Poly(L-lysine)(m)-b-poly[N-(N',N'-diisopropylaminoethyl) aspartamide](n) copolymers, abbreviated as PLLm-b-P[Asp(DIP)](n) were designed and synthesized via ring-opening polymerization(ROP), click chemistry, aminolysis and hydrolysis. Using H-1 NMR, FT-IR and GPC, the structures and compositions of these copolymers have been verified. Through feed ratio control, block copolymer PLLm-b-P[Asp(DIP)](n) with different PLL and PAsp(DIP) block lengths were obtained, which can be modified to adjust the pH responsiveness and the self-assembling behaviors of the PLLm-b-P[Asp(DIP)](n). From the results of DLS, TEM and H-1 NMR, these block copolymers can form stable micelles with a partially hydrated PAsp(DIP) core and a PLL corona at pH 7.4. While as demonstrated by H-1 NMR and TEM, these PLLm-b-P[Asp(DIP)](n) micelle was disassembled due to further protonation of the tertiary amine in the PAsp(DIP) block at pH 5.4. These pH responsive character of the PLLm-b-P[Asp(DIP)](n) micelles made them as potential pH responsive gene delivery system which may co-deliver drug and DNA simultaneously. (C) 2011 Elsevier Ltd. All rights reserved.