Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery |
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Authors: | Yaping Wang Songyue Cheng Wendi Fan Yikun Jiang Jie Yang Zaizai Tong Guohua Jiang |
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Affiliation: | 1. College of Materials Science and Engineering and Institute of Smart Biomedical Materials, Zhejiang Sci-Tech University, Hangzhou 310018, China;2. College of Science, Institute of Materials Physics and Chemistry, Nanjing Forestry University, Nanjing 210037, China |
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Abstract: | 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 H2O2-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 H2O2 and pH stimuli due to the chemical change of H2O2 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 H2O2) 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. |
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Keywords: | Diabetes Transcutaneous microneedles Stimuli-responsive drug release Hollow mesoporous silica nanoparticles Block copolymer |
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