Injectable dual glucose-responsive hydrogel-micelle
composite for mimicking physiological basal and prandial insulin delivery
Lv, J (Lv, Juan)[ 1 ] ; Wu, G (Wu, Gang)[ 1 ] ; Liu, Y (Liu, Ying)[ 1 ] ; Li, C (Li, Chang)[ 1 ] ; Huang, F (Huang, Fan)[ 3,4 ] ; Zhang, YM (Zhang, Yumin)[ 3,4 ] ; Liu, JJ(Liu, Jinjian)[ 3,4 ] ; An, YL (An, Yingli)[ 1 ] ; Ma, RJ (Ma, Rujiang)[ 1 ] ; Shi, LQ (Shi, Linqi)[ 1,2 ]
SCIENCE CHINA-CHEMISTRY, 2019, 62(5): 637-648 特刊: SI
DOI: 10.1007/s11426-018-9419-3
Abstract
For type 1
and advanced type 2 diabetic patients, insulin replacement therapy with
simulating on-demand prandial and basal insulin secretion is the best option
for optimal glycemic control. However, there is no insulin delivery system yet
could mimic both controlled basal insulin release and rapid prandial insulin release
in response to real-time blood glucose changes. Here we reported an artificial
insulin delivery system, mimicking physiological basal and prandial insulin
secretion, to achieve real-time glycemic control and reduce risk of
hypoglycemia. A phenylboronic acid (PBA)/galactosyl-based glucose-responsive
insulin delivery system was prepared with insulin-loaded micelles embedded in
hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles
could swell and achieve rapid glucose-responsive release of insulin, mimicking
prandial insulin secretion. When the glucose level returned to the normal
state, only the micelles partially responded to glucose and still released
insulin gradually. The hydrogel with increased crosslinking density could slow
down the diffusion speed of insulin inside, resulting in controlled release of
insulin and simulating physiological basal insulin secretion. This
hydrogel-micelle composite insulin delivery system could quickly reduce the
blood glucose level in a mouse model of type 1 diabetes, and maintain normal
blood glucose level without hypoglycemia for about 24 h. This kind of
glucose-responsive hydrogel-micelle composite may be a promising candidate for
delivery of insulin in the treatment of diabetes.
