pH and osmotic pressure inside biodegradable microspheres during erosion.
OBJECTIVE
To measure changes in pH as well as osmotic pressure in aqueous pores and cavities inside biodegradable microspheres made from polymers such as poly(D,L-lactic acid) (PLA) and poly(D,L-lactic acid -co- glycolic acid) (PLGA).


METHODS
The internal osmotic pressure inside eroding PLA microspheres was analyzed with differential scanning calorimetry (DSC) in a temperature range of 10 to--25 degrees C. The osmotic pressure was calculated from the melting peaks of the aqueous phase using purity analysis. For pH determination, PLGA microspheres were loaded with a pH-sensitive spin probe which allowed the determination of pH by electron paramagnetic resonance (EPR).


RESULTS
The osmotic pressure in PLA microspheres increased to 600 mOsm within four days and decreased to 400 mOsm after two weeks. The pH in PLGA microspheres in this study was < or =4.7. Basic drugs such as gentamicin free base or buffering additives led to a pH increase. In no case, however, did the internal pH exceed a value of 6 within 13 hours.


CONCLUSIONS
DSC and EPR are useful techniques to characterize the chemical microenvironment inside eroding microspheres. This data in combination with detailed information on peptide and protein stability could allow in the future to predict the stability of such compounds within degradable polymers.
Aventis Research & Technologies, Industriepark Hoechst, Frankfurt am Main, Germany.
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Brunner
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Mäder
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Göpferich
D000465:Algorithms; D001673:Biodegradation, Environmental; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D008863:Microspheres; D008956:Models, Chemical; D009997:Osmotic Pressure; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)