Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 495, Issue 1, Pages 171-178Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2015.08.044
Keywords
Peritoneal macrophages; Short interference RNA; pH-Sensitive cationic lipid; Multifunctional envelope-type nano device; Size; Administration route
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Funding
- Special Education and Research Expenses of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Japan Society for Promotion of Science (JSPS)
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Macrophages are key contributors to various inflammatory diseases. Therefore, the development of an efficient in vivo short interference RNA (siRNA) system that can be delivered to macrophages represents a novel treatment strategy for addressing these disorders. It was recently revealed that peritoneal macrophages (PEMs) are involved in several diseases including ovarian cancer, and are now recognized as a promising drug target. We report herein on the use of pH-sensitive cationic YSK05-MENDs as siRNA carriers and on the impact of both the size of the YSK05-MENDs and their administration routes for the efficient targeting PEMs to achieve a high level of gene silencing activity. The size of the YSK05-MENDs had a dramatic effect on their specificity for PEMs when administered intravenously, but not for intraperitoneal injection. Also, significant gene silencing was achieved by an intraperitoneal administration of the YSK05-MEND at a dose in the single digit mg/kg range. To our knowledge, this is the most efficacious method for siRNA delivery for gene silencing in PEMs in vivo reported to date. These findings enabled us to investigate the complex function of PEMs through several gene silencing simultaneously. (C) 2015 Elsevier B.V. All rights reserved.
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