title: Self-assembled micellar formulation of chafuroside A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.
abstract: Chafuroside A (CFA), a poorly water-soluble flavone C-glycoside, was firstly isolated from oolong tea, and it acts as a potent anti-inflammatory agent. The present study was undertaken to develop a water-soluble formulation of CFA using a self-assembled micellar (SAM) system, with the aim of improved dissolution behavior and potent anti-inflammatory effects. The SAM formulation of CFA (CFA/SAM) was characterized in terms of its morphology, particle size distribution, crystallinity, and dissolution behavior. In dissolution testing, the CFA/SAM exhibited marked improvement in dissolution behavior when compared with crystalline CFA, and then, nano-micellar particles were constituted with a mean diameter of 84 nm. The therapeutic potential of the crystalline CFA and CFA/SAM was assessed using an experimental asthma/chronic obstructive pulmonary disease (COPD)-like model. Orally-administered CFA at 0.5mg/kg or higher could attenuate inflammatory symptoms in a dose-dependent manner, as evidenced by decreases of infiltrated granulocytes, including macrophages and neutrophils, and myeloperoxidase, a specific biomarker for neutrophilia. Biomarker profiling demonstrated that the CFA/SAM at 0.1mg CFA/kg was equipotent to CFA at 1.0mg/kg in ameliorating antigen-induced airway inflammation, suggesting the better pharmacological effect of CFA/SAM due to improved dissolution behavior. From these observations, the SAM formulation might be an efficacious approach for enhancing the therapeutic potential of CFA for treatment of inflammatory diseases.
authors: Department of Pharmacokinetics and Pharmacodynamics, and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
authors: Satomi
authors: S
authors: Onoue
authors: Takuya
authors: T
authors: Matsui
authors: Yosuke
authors: Y
authors: Aoki
authors: Hitoshi
authors: H
authors: Ishida
authors: Haruo
authors: H
authors: Nukaya
authors: Keitatsu
authors: K
authors: Kou
authors: Shizuo
authors: S
authors: Yamada
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D055598:Chemical Phenomena; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006027:Glycosides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: C510948:3,4,11-trihydroxy-2-(hydroxymethyl)-8-(4-hydroxyphenyl)-3,4,4a,11b-tetrahydro-2H,10H-pyrano(2',3'-4,5)furo(3,2-g)chromen-10-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D047309:Flavones; D006027:Glycosides; D006576:Heterocyclic Compounds, 4 or More Rings; D008823:Micelles; D009195:Peroxidase