Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice

Autor: Kensuke Egashira, Akihito Yasuoka, Chisayo Kozuka, Hiroaki Masuzaki, Kaku Nakano, Ayano Kinjo, Keiko Abe, Takashi Kondo, Fukuda Kotaro, Chitoshi Takayama, Asuka Kamei, Chigusa Shimizu-Okabe, Morinaga Hidetaka
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Blood Glucose
Male
obesity
Time Factors
type 2 diabetes mellitus
Pharmaceutical Science
Administration
Oral
Mice
Obese
chemistry.chemical_compound
Polylactic Acid-Polyglycolic Acid Copolymer
Hypolipidemic Agents
Drug Carriers
Behavior
Animal
Phenylpropionates
nanotechnology
poly (dl-lactide-co-glycolide)
General Medicine
brown rice
Endoplasmic Reticulum Stress
Lipids
PLGA
medicine.anatomical_structure
Nanomedicine
Liver
Hypothalamus
Lipophilicity
Brown rice
Original Article
Research Article
medicine.medical_specialty
Materials science
Drug Compounding
γ-oryzanol
RM1-950
Drug Administration Schedule
03 medical and health sciences
Food Preferences
Islets of Langerhans
Internal medicine
medicine
Diabetes Mellitus
Animals
Hypoglycemic Agents
Technology
Pharmaceutical
therapeutic modality
Lactic Acid
Dose-Response Relationship
Drug
Pancreatic islets
Endoplasmic reticulum
Metabolism
Bioavailability
Gastrointestinal Microbiome
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
Intestinal Absorption
Solubility
Nanoparticles
Therapeutics. Pharmacology
Insulin Resistance
Energy Metabolism
Polyglycolic Acid
Zdroj: Drug Delivery, Vol 24, Iss 1, Pp 558-568 (2017)
Drug Delivery
article-version (VoR) Version of Record
ISSN: 1521-0464
1071-7544
Popis: Our previous works demonstrated that brown rice-specific bioactive substance, γ-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 γ-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of γ-oryzanol with super-high lipophilicity, we encapsulated γ-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 best-known severest diabetic model in mice. To our surprise, Nano-Orz markedly ameliorated fuel metabolism with an unexpected magnitude (∼1000-fold lower dose) compared with regular γ-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 γ-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.
Databáze: OpenAIRE
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