title: Evaluation of polyanion-coated biodegradable polymeric micelles as drug delivery vehicles.
abstract: Polymeric micelles, as drug delivery vehicles, must achieve specific targeting and high stability in the body for efficient drug delivery. We recently reported the preparation of polyanion-coated biodegradable polymeric micelles by coating positively charged polymeric micelles consisting of poly(L-lysine)-block-poly(L-lactide) (PLys-b-PLLA) AB diblock copolymers with anionic hyaluronic acid (HA) by polyion complex (PIC) formation. The obtained HA-coated micelles showed significantly higher stability in aqueous solution. In this study, to evaluate the HA-coated polymeric micelles as a drug carrier, model drug release from the micelles and cytotoxicity of the micelles were investigated. The HA-coated micelles showed sustained release of model drugs and low cytotoxicity. It is known that there are receptors for HA on liver sinusoidal endothelial cells (LSEC). Specific interactions of HA-coated micelles with LSECs and Kupffer cells were investigated and compared with polymeric micelles coated with other polyanionic polysaccharides, i.e., heparin (Hep) and carboxymethyl-dextran (CMDex). Although Hep-coated micelles and CMDex-coated micelles were incorporated into both Kupffer cells and LSECs, HA-coated micelles were taken up only into LSECs. These results suggest HA-coated micelles have potential utility as drug delivery vehicles exhibiting specific accumulation into LSECs.
authors.affiliation: Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. yohya@kansai-u.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohya
authors.forename: Shinya
authors.initials: S
authors.lastname: Takeda
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shibata
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ouchi
authors.forename: Arihiro
authors.initials: A
authors.lastname: Kano
authors.forename: Tomoki
authors.initials: T
authors.lastname: Iwata
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniwaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D006820:Hyaluronic Acid / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D000071228:Polyelectrolytes; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011107:Polylysine / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D006820:Hyaluronic Acid; D008823:Micelles; D004364:Pharmaceutical Preparations; D000071228:Polyelectrolytes; D011091:Polyesters; D011107:Polylysine; D011108:Polymers; C033616:poly(lactide)