Effect of Chitosan-Cysteine Conjugate on Enzymatic Degradation and Hypoglycemic effect of Insulin

Abstract

Abstract: Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate on enzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteine conjugate was synthesized. The protective effect of the conjugate against degradation of insulin by α-chymotrypsin and trypsin was evaluated in vitro. Insulin enteric-microspheres were prepared by using O1/O2 emulsion solvent evaporation method. The hypoglycemic enhancement effect of the conjugate was studied by oral administration of insulin solution or enteric-microspheres to rats. Results The thiol group content of the synthesized conjugate was about 200 μmol·g^-1 polymer, which showed a strong protective effect on insulin from enzymatic degradation in vifro. Almost all the insulin incubated in α-chymotrypsin solution or trypsin solution without chitosan-cysteine conjugate was degraded entirely within 1 h and 5 h respectively, whereas above 75% of insulin remained in the same content of the enzymatic solution containing 4 mg·mL^-1 conjugate. The drug loading of insulin enteric-microspheres was about 7%.In vivo experiment, chitesan-cysteine conjugate (85 mg·kg^-1) prolonged the hypoglycemic time of insulin solution or enter-ic-microspheres when administered simultaneously with the absorption enhancer SNAC. Conclusion Chitosan-cysteine con-jugate has a marked inhibitory effect on the enzymatic degradation of insulin in vitro, and it displays a significant hypoglyce-mic enhancement effect on insulin oral formulation in vivo.

Key words: chitosan-cysteine conjugate, chitosan-cysteine conjugate, insulin, insulin, enzymatic degradation, enzymatic degradation, enteric-microspheres, enteric-microspheres, hypoglycemic enhancement, hypoglycemic enhancement

CLC Number:

R944

R977.15

Supporting:

QI Rong, PING Qi-neng^*, XU Rui-yang, SHI Yong-ping. Effect of Chitosan-Cysteine Conjugate on Enzymatic Degradation and Hypoglycemic effect of Insulin[J]. .

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