pH-Sensitive Amphiphilic Biodegradable Graft Co-Polymer Aggregates Based on Polyaspartamide for Intracellular Delivery

A biodegradable, pH-sensitive amphiphilic co-polymer, o-(2-aminoethyl)-o'-methylpolyethylene glycol/1-(3-aminopropyl) imidazole/lactic acid oligomers-g-polyaspartamide (MPEG/API/LAs-g-PASPAM), was synthesized. The hydrophobic biodegradable poly(lactic acid) (PLA), the hydrophilic MPEG and the pH-sensitive API were successfully introduced into the biodegradable polysuccinimide (PSI) backbone by grafting. In its synthesis, the feed ratio of MPE to PLA was varied to provide different amphiphilic balances. FT-IR and H-1-NMR spectroscopy were used to identify the chemical structure of the MPEG/API/LAs-g-PASPAM co-polymers synthesized. Tens to a few hundreds of nanometer-scaled aggregates, appropriate for intracellular drug-carrier applications, were developed in the simulated buffer solution, and their self-assembling behavior was significantly affected by the environmental pH. The size and morphology of self-aggregates were investigated using dynamic light scattering and transmission electron microscopy. The buffering effect was observed in the endosomal pH range. The drug loading and release experiments were conducted for a series of co-polymer aggregate systems, and it was noted that the release behavior was mostly governed by diffusion. The biodegradable kinetics was also studied to ascertain the drug-release mechanism. (C) Koninklijke Brill NV, Leiden, 2011