pH-dependent self-assembly of amphiphilic poly(l-glutamic acid)-block-poly(lactic-co-glycolic acid) copolymers

A novel biodegradable AB-type diblock copolymer poly(L-lactic- co-glycolic acid)-block-poly(l-glutamic acid) (PLGA-b-PGA) was synthesized by a macromolecular coupling reaction between carboxyl-terminated PLGA and amino-terminated poly(γ-benzyl-glutamate) (PBLG) and the subsequent elimination of the protecting benzyl group. The structures of PLGA-PGA and its precursors were confirmed by Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). This synthetic strategy simplified a former synthesis process of polypeptide-poly(l-lactic acid)(PLA); by using this new synthetic route the molecular weight and block ratio of PLGA-PGA could be easily controlled by adjusting the chain length of PLGA/PGA. The pH sensitivity and self-assembly behavior of PLGA-PGA copolymer were investigated by environmental scanning electron microscopy (ESEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The results showed that the copolymer exhibited high pH responses, and the morphologies of the copolymer aggregates underwent four stages orderly with the pH increase (pH = 3-9): a disorganized form, micelles, semi-vesicles with thick walls and vesicles. Such a pH-dependent self-assembly process of the copolymer is promising for drug control release and bio-applications.