Controlled release of a model protein lysozyme from phase sensitive smart polymer systems

The purpose of this study was to investigate the suitability of phase sensitive smart polymer-based protein formulations in order to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time. Four different formulations, using D,L-poly(lactide) (D,L-PLA) and a solvent mixture of different ratios of benzyl benzoate (BB) and benzyl alcohol (BA), were prepared. Conformational stability and biological activity of lysozyme were studied by differential scanning calorimeter and enzyme activity assay, respectively. We found a significant (P < 0.05) increase in burst and rate of release of incorporated lysozyme from formulations containing greater proportion of BA. In order to increase the conformational stability and biological activity of lysozyme, we incorporated mannitol as stabilizer into formulations. Mannitol increased the conformational and biological activity of lysozyme in comparison to the control formulation prepared without mannitol. In conclusion, phase sensitive smart polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time.