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.
Delivery of therapeutic protein drugs is a hot issue in the clinical application, because protein drugs have low side effects and highly therapeutic effects compared with chemical drugs. Despite their prominent advantages, protein drugs have high risk for human therapy such as their easy degradation by proteolytic enzymes, renal filtration and immune response. Over the past few decades, a large number of polysaccharides as vehicles for the protein delivery system have been developed to overcome the problems. This review presents the studies on protein delivery based on polysaccharides used as stabilizer and vehicles comprising nano-or microspheres to overcome inherent limitations of therapeutic proteins.
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