期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 3, 期 4, 页码 572-578出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.6b00716
关键词
glucose-responsive drug delivery; type I diabetes; enzyme mimetics; ceria nanoparticles; mesoporous silica
资金
- National Research Foundation under the Ministry of Science, ICT and Future Planning [2010-0027955, 2015RIA2A2A01005548]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare Republic of Korea [HI14C0211]
- Korea Health Promotion Institute [HI14C0211020016] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2015R1A2A2A01005548, 2010-0027955] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A glucose-responsive closed-loop insulin delivery system represents an ideal form of treatment for type 1 diabetes mellitus. Here, we develop a glucose-responsive protein delivery system based on chitosan microgels loaded with enzyme mimicking inorganic nanoparticles. The pH-sensitive chitosan microgels, integrated with glucose-mediated pH-lowering enzymatic large-pore mesoporous silica (MCF), were fabricated via an electrospray process. Ceria nanoparticles (CeNPs), which is a catalase-mimicking inorganic artificial enzyme with a substantial stability compared to that of catalase, were incorporated into the MCF along with glucose oxidase. In hyperglycemic conditions, CeNPs successfully decomposed the toxic hydrogen peroxide that was generated from the glucose oxidation reaction mediated by glucose oxidase and regenerate oxygen; this protected glucose oxidase from denaturation. The pH-lowering induced by the enzymatic MCF in high glucose concentration resulted in swelling of the chitosan microgels and the subsequent release of the encapsulated model protein drug, such as bovine serum albumin and insulin. Finally, we successfully demonstrated self-regulated repetitive protein release from the chitosan microgels, which showed a basal release rate under normoglycemic conditions and an enhanced release rate under hyperglycemic conditions.
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