Semisolid, self-catalyzed poly(ortho ester)s as controlled-release systems: protein release and protein stability issues
Research output: Contribution to journal › Journal article › peer-review
Semisolid, self-catalyzed poly(ortho ester)s (POEs), are investigated as potential sustained-release systems for proteins. In this study, some factors influencing protein release kinetics and protein instability were evaluated. As model proteins, lysozyme, alpha-lactalbumin, bovine serum albumin, and vascular endothelial growth factor, which were lyophilized from various buffer solutions in the absence and presence of lyoprotectants, were used. For all protein formulations, the release kinetics followed the visually observed polymer dissolution profile. In the absence of any buffers in the protein formulation, the release was continuous. Formulations containing a buffer below pH 7 accelerated POE degradation, resulting in faster protein release. In contrast, a strong buffer capacity at pH 7 reduced the POE degradation and resulted in a biphasic release pattern. Moreover, proteins with a high isoelectric point (pI > 7) appeared to catalyze the POE degradation, and the effect of the buffer strength and pH was much smaller than for proteins with low pI (<7). In the absence of lyoprotectants, all proteins tested showed an increasing fraction of covalent protein aggregates during the release. Protein formulations containing a lyoprotectant, such as sucrose or trehalose, did not show a significantly increased aggregation, whereas there was a minor influence of the large solid loadings on the release kinetics. In conclusion, this semisolid, self-catalyzed POE showed good promise as a sustained-release matrix for bioactive proteins.
|Journal||Journal of Pharmaceutical Sciences|
|Number of pages||10|
|Publication status||Published - Apr 2002|