論文 - 詳細
| RRC ID | 18221 |
|---|---|
| 著者 | Onoue S, Kuriyama K, Uchida A, Mizumoto T, Yamada S. |
| タイトル | Inhalable sustained-release formulation of glucagon: in vitro amyloidogenic and inhalation properties, and in vivo absorption and bioactivity. |
| ジャーナル | Pharm Res |
| Abstract |
PURPOSE:The present study aimed to develop novel glucagon-loaded PLGA nanospheres without cytotoxic fibril formation for chronic glucagon replacement therapy. METHODS:Glucagon-loaded nanospheres (GLG/NS) were prepared by an emulsion solvent diffusion method in oil, and a respirable powder formulation (GLG/NS-RP) was prepared with a jet mill. Physicochemical and inhalation properties of GLG/NS-RP were characterized, and pharmacokinetic behavior and hyperglycemic effect of intratracheally instilled GLG/NS-RP were evaluated in rats. RESULTS:Although preparation of GLG/NS using glucagon solution at concentrations over 10 mg/mL led to significant formation of cytotoxic glucagon aggregates, glucagon solution at less than 5 mg/mL did not cause structural changes. Drug release behavior of GLG/NS showed a biphasic pattern with an initial burst and slow diffusion. Laser diffraction and cascade impactor analyses of GLG/NS-RP suggested high dispersion and deposition in the respiratory organs with a fine particle fraction of 20.5%. After the intratracheal administration of the GLG/NS-RP (200 μg glucagon/kg) in rats, glucagon was released in a sustained manner, leading to sustained hyperglycemic effects compared with those of normal glucagon powder. CONCLUSION:These data would suggest a therapeutic benefit of the newly developed GLG/NS-RP as an alternative to the injection form of glucagon currently used. |
| 巻・号 | 28(5) |
| ページ | 1157-66 |
| 公開日 | 2011-5-1 |
| DOI | 10.1007/s11095-011-0379-8 |
| PMID | 21287249 |
| MeSH | Animals Cell Line, Tumor Delayed-Action Preparations / chemistry* Dry Powder Inhalers / methods* Glucagon / administration & dosage* Glucagon / adverse effects Glucagon / pharmacokinetics* Glucagon / pharmacology Humans Lactic Acid / chemistry* Male Nanospheres / chemistry* Polyglycolic Acid / chemistry* Polylactic Acid-Polyglycolic Acid Copolymer Rats Rats, Wistar |
| IF | 3.242 |
| 引用数 | 12 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |