A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein

a glucose-mediated dual-responsive drug delivery system

which combines pH- and H

2

O

2

-responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch

has been developed to achieve self-regulated administration. The poly[4-(4

4

5

5-tetramethyl-1

3

2-dioxaborolan-2-yl)benzyl acrylate

]

-

b

-poly[2-(dimethylamino)ethyl methacrylate

]

(PPBEM-

b

-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast

the drug release rate is significantly enhanced upon H

2

O

2

and pH stimuli due to the chemical change of H

2

O

2

sensitive PPBEM block and acid responsive PDM block. Therefore

incorporation of anti-diabetic drug and glucose oxidase (GOx

which can oxidize glucose to gluconic acid and

in-situ

produce H

2

O

2

) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both

in vitro

and

in vivo

results show this MN device presents a glucose mediated self-regulated drug release characteristic

which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.