Preparing polymer-based sustained-release systems without exposing proteins to water-oil or water-air interfaces and cross-linking reagents.
We report a method to load proteins into polymer-based sustained-release systems without exposing them to water-oil or water-air interfaces, factors known to denature proteins. By dispersing a dextan solution containing a protein into a PEG solution containing small amount of alginate, a stable aqueous-aqueous "emulsion" was formed. The poly-anionic alginate generated a diffuse double layer around each dextran droplet to prevent them from contacting with each other and fusing to a block phase. Proteins distributed in the stabilized dextran droplets by preferential partition favoring dextran. Freeze-drying this emulsion resulted in protein-loaded dextran particles, 1-2 microm in diameter and 1.6 g/cm(3) in density. The particles were harvested by washing the lyophilized powder using organic solvents to remove the PEG continuous phase. An activity assay of encapsulated beta-galactosidase indicated that protein activity was preserved during the particle-forming process including the step of sonicating the particles in organic solvents. The dextran particles also improved release profile and integrity of proteins when encapsulated in degradable polymer sustained-release systems. The aqueous-aqueous emulsion offers a convenient way to prepare solvent-resistant protein-polysaccharide particles that can easily be incorporated in a variety of polymer-based pharmaceutical dosage forms and medical devices such as microspheres, scaffolds and drug-eluting stents for sustained-release protein delivery.
Jin
Tuo
T
Shanghai JiaoTong University School of Pharmacy, China. tjin@sjtu.edu.cn
Zhu
Jiahao
J
Wu
Fei
F
Yuan
Weien
W
Geng
Lee L
LL
Zhu
Hua
H
D000388:Air; D002152:Calorimetry, Differential Scanning; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D004655:Emulsions; D008863:Microspheres; D009211:Myoglobin / Q000737:chemistry*; D009821:Oils; D011092:Polyethylene Glycols / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D014867:Water; D014961:X-Ray Diffraction; D001616:beta-Galactosidase / Q000378:metabolism
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003911:Dextrans; D004655:Emulsions; D009211:Myoglobin; D009821:Oils; D011804:Quinolines; D014867:Water; D011092:Polyethylene Glycols; C047117:bicinchoninic acid; D001616:beta-Galactosidase