論文 - 詳細
| RRC ID | 57762 |
|---|---|
| 著者 | Ando H, Abu Lila AS, Fukushima M, Matsuoka R, Shimizu T, Okuhira K, Ishima Y, Huang CL, Wada H, Ishida T. |
| タイトル | A simplified method for manufacturing RNAi therapeutics for local administration. |
| ジャーナル | Int J Pharm |
| Abstract |
RNA interference (RNAi) is one of the most promising strategies for cancer therapeutics. The successful translation of RNAi therapeutics to a clinic setting requires a delivery system that is efficient and simple to upscale. In this study, we devised a simple industrial method to manufacture lipoplex, which includes short hairpin RNA against the expression of thymidylate synthase (TS shRNA) - a key molecule for DNA biosynthesis. An aqueous solution of TS shRNA was gently mixed with either a precursor of cationic liposome (Presome DF-1) or a cationic lipid mixture in an o/w emulsion. This solution was subsequently lyophilized under optimal conditions to obtain either FD-lipoplex-1 or FD-lipoplex-2, respectively. With this method, a lipoplex in activated form was obtained via a simple "one-step" hydration with saline. Both forms of FD-lipoplex showed physicochemical properties comparable to those of conventional lipoplex. FD-lipoplexes stably retained TS shRNA within their formulations in the presence of tumor ascites fluid. Intraperitoneal treatment with either FD-lipoplex-1 or FD-lipoplex-2 provided a therapeutic level of efficacy comparable to that of conventional lipoplex in the treatment of a peritoneal disseminated gastric cancer mouse model. Collectively, established freeze-drying-based methods for RNAi-therapeutic preparation could realistically be used in a clinical setting for the treatment of patients with peritoneal disseminated cancer. |
| 巻・号 | 564 |
| ページ | 256-262 |
| 公開日 | 2019-6-10 |
| DOI | 10.1016/j.ijpharm.2019.04.054 |
| PII | S0378-5173(19)30313-8 |
| PMID | 31015002 |
| MeSH | Animals Cell Line, Tumor Freeze Drying Humans Liposomes Male Mice, Inbred BALB C Mice, Nude Peritoneal Neoplasms / genetics Peritoneal Neoplasms / therapy* RNA Interference RNA, Small Interfering / administration & dosage* RNA, Small Interfering / chemistry RNAi Therapeutics Stomach Neoplasms / genetics Stomach Neoplasms / therapy* Thymidylate Synthase / genetics* |
| IF | 4.845 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |