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 1H 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 1H 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 1H 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.