Journal
DRUG DELIVERY
Volume 24, Issue 1, Pages 558-568Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2017.1279237
Keywords
Type 2 diabetes mellitus; brown rice; gamma-oryzanol; nanotechnology; poly(DL-lactide-co-glycolide); obesity; therapeutic modality
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Funding
- Japan Society for the Promotion of Science (JSPS
- KAKENHI) [15K19520, 24591338]
- Council for Science, Technology and Innovation (CSTI)
- Cross-ministerial Strategic Innovation Promotion Program (SIP), Technologies for creating next-generation agriculture, forestry and fisheries''
- Lotte Foundation
- Japan Foundation for Applied Enzymology
- New Energy and Industrial Technology Development Organization (NEDO)
- Promotion Project of Medical Clustering of Okinawa prefecture
- Okinawa Prefecture for Promotion of Advanced Medicine
- Grants-in-Aid for Scientific Research [17K09839, 16J40160, 15K19520, 17H01962, 17K07078] Funding Source: KAKEN
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Our previous works demonstrated that brown rice-specific bioactive substance, gamma-oryzanol acts as a chaperone, attenuates exaggerated endoplasmic reticulum (ER) stress in brain hypothalamus and pancreatic islets, thereby ameliorating metabolic derangement in high fat diet (HFD)induced obese diabetic mice. However, extremely low absorption efficiency from intestine of gamma-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of gamma-oryzanol with super-high lipophilicity, we encapsulated gamma-oryzanol in polymer poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Nano-Orz), and evaluated its metabolically beneficial impact in genetically obese-diabetic ob/ob mice, the bestknown severest diabetic model in mice. To our surprise, Nano-Orz markedly ameliorated fuel metabolism with an unexpected magnitude (similar to 1000-fold lower dose) compared with regular gamma-oryzanol. Furthermore, such a conspicuous impact was achievable by its administration once every 2 weeks. Besides the excellent impact on dysfunction of hypothalamus and pancreatic islets, Nano-Orz markedly decreased ER stress and inflammation in liver and adipose tissue. Collectively, nanotechnology-based developments of functional foods oriented toward gamma-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.
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