title: Chondroitin sulfate capsule system for efficient and secure gene delivery.
abstract: OBJECTIVE
  In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery.
  
  
  METHODS
  To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes.
  
  
  RESULTS
  The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes.
  
  
  CONCLUSIONS
  These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Kayo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002412:Cations; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000502:physiology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006461:Hemolysis; D008081:Liposomes; D008239:Lysine / Q000031:analogs & derivatives; D008546:Melanoma, Experimental; D051379:Mice; D010714:Phosphatidylethanolamines; D010957:Plasmids; D011095:Polyethylenes; D000644:Quaternary Ammonium Compounds; D014162:Transfection
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011095:Polyethylenes; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; D002809:Chondroitin Sulfates; D001120:Arginine; D008239:Lysine