PT  - JOURNAL ARTICLE
AU  - Weiqi Lu
AU  - Tae Gwan Park
TI  - Protein Release from Poly(lactic-co-glycolic acid) Microspheres: Protein Stability Problems
DP  - 1995 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 13--19
VI  - 49
IP  - 1
4099  - http://journal.pda.org/content/49/1/13.short
4100  - http://journal.pda.org/content/49/1/13.full
SO  - PDA J Pharm Sci Technol1995 Jan 01; 49
AB  - The enzyme, carbonic anhydrase, has been incorporated within poly(lactic-co-glycolic acid) microspheres using a double emulsion and solvent evaporation technique. The protein stability problems during the microsphere formulation procedure and during the release period were examined in relation to the protein release kinetics over a 2 month period. Different protein release profiles could be obtained depending on the polymers used. The protein release kinetics exhibited an initial fast release followed by a slow release, resulting in an incomplete protein release although the microspheres degraded significantly. The very slow release kinetics were attributed to the protein aggregation and non-specific adsorption within the microspheres. It was found that the protein was significantly denatured and aggregated during the double emulsion formulation step. Several excipients such as albumin, poly (ethylene oxide), Pluronic F-127, and gelatin, which were loaded along with the protein within microspheres, demonstrated better protein release kinetics partly due to an increase in the protein stability. The released protein from these fast degrading microspheres, however, was severely hydrolyzed and lost its catalytic activity, caused by the accumulation of degradation products in the medium.