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

J. Slager, A. J. Domb

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 1-3μm 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.

Original languageEnglish
Pages (from-to)4389-4396
Number of pages8
Issue number22
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by Polygene Ltd and Efrat Biopolymers Ltd.


  • Diastereoisomers
  • Insulin release
  • Polylactide
  • Stereocomplex


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