Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

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.

Polymer-grafted hollow mesoporous silica nanoparticles integrated with microneedle patches for glucose-responsive drug delivery

A glucose-mediated drug delivery system would be highly satisfactory fordiabetes diagnosis since it can intelligently release drug based on blood glucose levels.Herein,a glucose-responsive drug delivery system by integrating glucose-responsivepoly(3-acrylamidophenylboronic acid)(PAPBA)functionalized hollow mesoporous silicananoparticles(HMSNs)with transcutaneous microneedles(MNs)has been designed.Thegrafted PAPBA serves as gatekeeper to prevent drug release from HMSNs atnormoglycemic levels.In contrast,faster drug release is detected at a typicalhyperglycemic level,which is due to the change of hydrophilicity of PAPBA at highglucose concentration.After transdermal administration to diabetic rats,an effectivehypoglycemic effect is achieved compared with that of subcutaneous injection.Theseobservations indicate that the designed glucose-responsive drug delivery system has apotential application in diabetes treatment.