Monitoring microviscosity and microacidity of the albumin microenvironment inside degrading microparticles from poly(lactide-co-glycolide) (PLG) or ABA-triblock polymers containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethyleneoxide) B blocks.
OBJECTIVE
The purpose of this study was to monitor the microenvironment of an encapsulated model protein during the release from biodegradable microparticles (MP) made from three different polymers, namely poly(lactide-co-glycolide) (PLG) and ABA-triblock polymers containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethyleneoxide) B blocks with an A:B ratio of 90:10 (ABA1O) and 70:30 (ABA30).


METHODS
MP loaded with spin labeled albumin were prepared by a w/o/w technique. The particles were characterized by light scattering and electron microscopy. In vitro release of albumin was determined by size exclusion chromatography. Light microscopic experiments were conducted to visualize water penetration in the matrix. The protein microenvironment inside the degrading microparticles was characterized noninvasively by 2 GHz EPR spectroscopy.


RESULTS
Water penetrated rapidly into all MP in the range of few minutes. A burst release was observed for PLG. The release from ABA block-polymers continued for over 14 days despite the rapid solubilization of the protein inside the microparticles. The initial microviscosity of the protein environment inside the ABA particles after exposure to buffer was 2 mm2/s and increased with time. A gradual decrease of the pH to a value of 3.5 was observed within the MP.


CONCLUSIONS
The data indicate that the microviscosity and microacidity inside protein loaded microparticles can be studied nondestructively by EPR spectroscopy. Our results clearly demonstrate that ABA-block polymers are superior to PLG allowing a controlled release of proteins from swollen microspheres.
Mäder
K
K
Department of Pharmaceutics and Biopharmacy, Philipps-University Marburg, Germany.
Bittner
B
B
Li
Y
Y
Wohlauf
W
W
Kissel
T
T
D000418:Albumins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D013113:Spin Labels; D014783:Viscosity
D000418:Albumins; D011095:Polyethylenes; D013113:Spin Labels; D011098:Polyglactin 910