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
リソース情報
ヒト・動物細胞 MKN45(RCB1001)