Improvement of protein loading and modulation of protein release from poly(lactide-co-glycolide) microspheres by complexation of proteins with polyanions

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Abstract
A novel method was proposed to incorporate and modulate protein release from poly(lactide-co-glycolide) (PLGA) microspheres by a modified w/o/w emulsion solvent evaporation technique with poly(methacrylic acid) (PMAA)/insulin complex suspension as the inner aqueous phase instead of the neat protein solution. It was found that a reversible, water-insoluble complex could be formed between PMAA and insulin by electrostatic interactions. A great increase in insulin entrapment efficiency was observed as the PMAA/insulin complex was adopted to prepare PLGA microspheres. A large number of the complex particles adsorbed at the surface of the microspheres, resulting in the more rapid insulin release. The complexation and microencapsulation processes have little effect on insulin bioactivity, which was revealed by examination of the plasma glucose levels of the diabetic rats administrated with the microspheres.

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