Stereocomplexes based on poly(lactic acid) and insulin: formulation and release studies
Diastereoisomeric complexes of insulin with d-poly(lactic acid) (d-PLA) or stereocomplexes of d- and l-PLA entrapping insulin were discovered. The complexes were spontaneously formed when insulin and d-PLA were mixed together in acetonitrile solution. Complexes of insulin–d-PLA formed a microparticulate precipitate after a few hours in the solution. The porous 1–3 μm precipitate, which contained both insulin and d-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. l-PLA or d,l-PLA did not form a precipitate with insulin, which indicates stereospecificity to the complex formation. Microparticulates were also obtained when l-PLA was added to the d-PLA–insulin solution. In this case two types of complexes, d-PLA–insulin and d-PLA–l-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.
Journal: Biomaterials - Volume 23, Issue 22, November 2002, Pages 4389–4396