Controlled insulin delivery systems serving as an artificial pancreas have the potential for revolutionizing the treatment of diabetes and became one of the most sought after achievements in the medical science field. [1] Many systems have been studied to controlled the release of insulin such as an oral delivery system for therapeutic insulin based on the protected insulin from the enzymatic degradation in the gastric fluid by using poly(methacrylic acid) grafted with poly(ethylene glycol) [2] as the carrier. Nasal insulin delivery system using the microsphere of aminated gelatin [3] and poly(methacrylic acid)-poly(ethylene glycol) [4] to encapsulated the drug. Chiou [5] presented the systemic delivery of insulin through the eyes. Although promising results have been achieved with chemical drug delivery systems, inadequate insulin release, and stability issues remain critical impedimenta for controlling the blood glucose level in diabetic patients. The primary disadvantage is that the systems require single or multiple daily therapies.

Here, we report a new insulin delivery system based of the novel pH/temperature sensitive injectable hydrogel. The new concept of this system is using poly(b-amino ester) (PAE) as duo-functional group. Firstly, PAE is used as a pH sensitive moiety [6] to produce a new polymeric material of which aqueous solutions undergo sol-gel transition by pH change, as well as by temperature change. The second is using this block copolymer to encapsulate insulin by the ionic lick between the positive charges of PAE negatively charged of insulin. The release of insulin can controlled by degradation of pH sensitive moiety, poly(b-amino ester) that can be easily degrade within two or three weeks and demonstrated lower glucose level in diabetic animal. The accommodation of the characteristics into insulin delivery systems resulted in the sustained zero-order drug release with insulin concentration in plasma on Female Sprague-Dawley (SD) rats and continuous blood glucose normalization in streptozotocin-induced diabetic rats.

This work was supported by Korea Research Foundation Grant KRF-2006-005-J04602.

Keywords: Insulin; pH sensitive hydrogel; temperature sensitive hydrogel; b-amino ester.

REFERENCES

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