title: Preparation of calcium phosphate nanocapsule including deoxyribonucleic acid-polyethyleneimine-hyaluronic acid ternary complex for durable gene delivery.
abstract: Our plasmid delivery systems comprising deoxyribonucleic acid (DNA), polyethyleneimine (PEI), and hyaluronic acid (HA) have already achieved the high-extragene expression in tumor tissues. Repeated transfection with certain cytokine genes effectively induced tumor regression and complete disappearance of the tumor in some cases. Frequent injection is sometimes difficult depending on the tumor site. However, single injection often leads to an unsatisfactory efficacy owing to the short duration of the gene expression. In this study, we prepared calcium phosphate (CaP) nanocapsule including plasmid DNA complexes as a durable gene transfection system, which would be slowly degraded, and release DNA complex in the body. CaP nanocupsule including DNA complexes with a diameter of approximately 200 nm was prepared by immersing HA-coated DNA-PEI complex in simulated body fluid. It showed gene expression in cultured cells with duration longer than 2 weeks. By this slow-releasing system, significant tumor-growth suppression and, finally, complete tumor disappearance were observed after single injection into the tumor. Capsulated DNA complex with Ca thus seems promising as a sustained gene expression device.
authors.affiliation: Musashino University, Research Institute of Pharmaceutical Sciences, Nishitokyo, Tokyo, 202-8585, Japan; Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, Clinical Medical-Engineering Laboratory, Higashimurayama, Tokyo, 189-0021, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Koyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000737:chemistry*; D007267:Injections / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects; D008546:Melanoma, Experimental; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods
chemical_list: D002130:Calcium Phosphates; D053769:Nanocapsules; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D004247:DNA; C020243:calcium phosphate
keywords: DNA complex; calcium phosphate; durable gene expression; gene therapy; nanocapsuls; nanoparticles; non-viral gene delivery; plasmid DNA