| Objective:Diabetes mellitus is a kind of metabolic disease with high blood glucose.So the blood glucose is controlled by injecting insulin.This is very inconvenient for patients and can not offer a kind of secrete model of physiological insulin.It is important to note that it can't prevent the complications from happening, such as cardiovascular disease,nephropathy,retinopathy,neuropathy and so on. Therefore,it is significant to develop a kind of glucose-responsive system applyed for self-release of insulin.The materials with aminobenzeneboronic acid groups have glucose responsivity, which can be used as an insulin release carrier.To obtain a novel glucose sensitive materials,herein,aminobenzeneboronic acid was introducted into chitosan backon. Meanwhile,its nanoparticles were prepared by self-assembly,and the glucose responsivity was evaluated and the preliminary cell viability of the materials was also evaluated.And the physicochemical properties of insulin-loaded PBACS nanoparticles were characterized and insulin release in vitro was further investigated at different glucose concentrations.In the present study,we further evaluated PBACS materials used for the formation of the bioartificial pancreas with glucose sensitivity.Methods:1.Aminobenzeneboronic acid was grafted to chitosan via amidocarbonylation reactions between the carboxylic group and a free primary amino group.The material was characterized by ~1H NMR,FTIR,EA and GTA.2.Nanoparticles were prepared by self-assembly.The physicochemical properties of the nanoparticles were evaluated by TEM,DSL and Zeta Potential.And the insulin loading efficiency and the behavior of insulin release in response to changes in the concentration of glucose were further investigated.3.To access the biocompatibility of PBACS,in vitro cell biocompatibility on mouse insulinoma cells was evaluated.4.The bioactivity of insulin was also investigated by circular dichroism spectra.5.To prepare glucose responsive microcapsules and detect its function.Meanwhile, the glucose-responsive biomicrocapsules were constructed by encapsulatingβ-TC3. The cell proliferation and the cell activity recovery after freezing the biomicrocapsule were further studied.Resu Its:1.The glucose-responsive PBACS materials were successfully prepared,which was proved through IR and ~1H NMR.Self-assembled nanoparticles were in the size range of 500～690nm,with positive charge(+2.76 to +5.24mV) and the dispersibility is good.Drug loading efficiency is high up to 18%.The nanoparticles have good biocompatibility and glucose responsivity in the range of glucose concentration(0 to 3 mg/ml).2.Insulin release in vitro shows it has two-phase model.The nanoparticle rapidly releases insulin to reach the effective concentration in midvelocity infiltration phase and polymeride degradation phase,it last 48 hours.In addition,the secondary structures of insulin as determined by CD spectra were preserved in all formulations.3.Glucose-responsive microcapsules(AmCA) were prepared by layer-by-layer. self assembly of polyelectrolytes(modified chitosan and alginate).The results show it had good mechanical strength,biocompatiblility and glucose responsivity.4.Biomicrocapsules encapsulatedβ-TC3 by using modified chitosan and alginate polyelectrolytes were prepared,and it well promoted cell proliferation.In addition, the results show that it is a kind vector ofβTC-3 cryopreservation and did not effect the cell viability after recovery compare with cell unencapsulated.Conclusion:1.The glucose-responsive PBACS has favourable biocompatibility and glucose sensitivity.It can be used for the controlled release of insulin.2.The glucose responsive bioartificial pancreas has been formulated and has good machinical stability,immunoisolation effect,glucose sensitivity and biocompatibility. It can physiologically simulate the insulin secretory behavior and a new promising vehicle for controlled insulin release.
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