Modulated insulin permeation across a glucose-sensitive polymeric composite membrane.

A glucose-sensitive polymeric composite membrane was prepared based on our previously developed stimuli-responsive membrane system. Membranes were cast from a mixture of glucose oxidase (GOD), catalase, and poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAm/MAA)) nanoparticles dispersed in a solution of a hydrophobic polymer. High efficiency of enzyme immobilization was achieved with undetectable leakage. The bioactivity of the immobilized GOD, as measured by pH change of glucose solutions, was found to be equivalent to approximately 80% of that of the free GOD. The addition of catalase markedly increased the oxidation rate of glucose. However, an optimal unit ratio of GOD to catalase and optimal enzyme loading were observed. The rate of insulin permeation through the membrane was modulated by glucose concentration due to shrinking or swelling of the embedded pH-sensitive nanoparticles. The response of insulin permeability to the change in the glucose concentration could be detected within 5-15 min. The permeability of insulin increased more than 3-fold as the glucose concentration was raised from 50 to 200 mg/dl. The average insulin permeability at 400 mg/dl of glucose was 8-fold that at 50 mg/dl in a continuous test in saline and was 6-fold in a three-cycle discontinuous test in pH 7.4 buffer.