| RRC ID |
57762
|
| Author |
Ando H, Abu Lila AS, Fukushima M, Matsuoka R, Shimizu T, Okuhira K, Ishima Y, Huang CL, Wada H, Ishida T.
|
| Title |
A simplified method for manufacturing RNAi therapeutics for local administration.
|
| Journal |
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.
|
| Volume |
564
|
| Pages |
256-262
|
| Published |
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
|
| Times Cited |
2
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001) |
