TY - JOUR
T1 - Stereocomplexes based on poly(lactic acid) and insulin
T2 - Formulation and release studies
AU - Slager, J.
AU - Domb, A. J.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Diastereoisomers
KW - Insulin release
KW - Polylactide
KW - Stereocomplex
UR - http://www.scopus.com/inward/record.url?scp=0036348416&partnerID=8YFLogxK
U2 - 10.1016/S0142-9612(02)00179-5
DO - 10.1016/S0142-9612(02)00179-5
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C2 - 12219829
AN - SCOPUS:0036348416
SN - 0142-9612
VL - 23
SP - 4389
EP - 4396
JO - Biomaterials
JF - Biomaterials
IS - 22
ER -