Stereocomplexes based on poly(lactic acid) and insulin: formulation and release studies

Diastereoisomeric complexes of insulin with -poly(lactic acid) ( -PLA) or stereocomplexes of - and -PLA entrapping insulin were discovered. The complexes were spontaneously formed when insulin and -PLA were mixed together in acetonitrile solution. Complexes of insulin– -PLA formed a microparticulate precipitate after a few hours in the solution. The porous 1–3 μm precipitate, which contained both insulin and -PLA, was insoluble in solvents that dissolve isotactic PLA, and had an additional transition temperature at 169°C. When suspending these particles in buffer solution of pH 7.4, 37°C, insulin was constantly released for a few weeks. -PLA or , -PLA did not form a precipitate with insulin, which indicates stereospecificity to the complex formation. Microparticulates were also obtained when -PLA was added to the -PLA–insulin solution. In this case two types of complexes, -PLA–insulin and -PLA– -PLA complexes, were formed. These macromolecular stereocomplexes may form the onset of the development of a new generation of controlled release systems for peptides and proteins, by molecular complexation with enantiomeric polymers.