Succinylated polysaccharide-based thermosensitive polyelectrostatic complex for protein drug delivery

The objective of this study was to develop a thermosensitive polyelectrostatic complex, based on polysaccharides, as carriers for long-term protein delivery. We developed a thermosensitive polyelectrostatic complex formed through combined electrostatic and hydrophobic interactions. The copolymer (succinylated pullulan -poly(l-lactide)) showed thermosensitivity in aqueous solution and complexed with protein (lysozyme) via electrostatic attractions and hydrophobic interactions at physiological temperature which formed a thermosensitive polyelectrostatic complex. The particle size of the thermosensitive polyelectrostatic complex was decreased from ~520 nm at 4°C to ~190 nm at 37.5°C. These thermosensitive polyelectrostatic complexes were stable in serum and salt conditions, and maintained the bioactivity of encapsulated protein for 36 days. The thermosensitive polyelectrostatic complex had prolonged in vivo stability that was greater than the polyelectrostatic complex. Based on stability and bioactivity tests for the lysozyme-loaded thermosensitive polyelectrostatic complexes, the potential of the long-term protein delivery carrier in physiological conditions was confirmed.