Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres by novel viscous S/W/O/W method.
In stabilizing proteins during microsphere fabrication, the viscous solid-in-water-in-oil-in-water (S/W/O/W) method was compared to the conventional multi-emulsion W/O/W and S/O/W method. Solid proteins lyophilized with cyclodextrin derivatives and polyethylene glycol (PEG) pass through an organic solvent phase and are then embedded in aqueous microdroplets of first emulsion. Proteins were stabilized at the water/organic solvent interface by an internal aqueous phase containing viscous polysaccharides, and then can be safely encapsulated without degradation. In addition, these microspheres showed a long-term protein release followed by nearly zero-order kinetics with minimal initial burst. This means that the viscous S/W/O/W method provides a safe strategy for microsphere fabrication and has promising properties, involving the preservation of protein bioactivity, the inhibition of protein denaturation or agglomeration, and long-term protein release.
Lee
Eun Seong
ES
Pharmaceutical & Health Research Institute, Amore Pacific Corporation, R&D Center, 314-1 Bora-dong, Giheung-gu, Yongin 446-729, Republic of Korea. hejulu@hanmail.net
Kwon
Min Jung
MJ
Lee
Hyeok
H
Kim
Jung Ju
JJ
D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D005612:Freeze Drying; D008863:Microspheres; D009113:Muramidase / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D014783:Viscosity
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004655:Emulsions; D011506:Proteins; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D009113:Muramidase