title: Effective drug delivery system for duchenne muscular dystrophy using hybrid liposomes including gentamicin along with reduced toxicity.
abstract: It is known that gentamicin (GM) could be a possible treatment for Duchenne Muscular Dystrophy (DMD). However, GM therapy has been hindered by several problems such as severe side effects of GM. In order to resolve these problems, we developed the drug delivery system (DDS) of GM using hybrid liposomes (HL) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23) lauryl ether (C₁₂(EO)₂₃). The hydrodynamic diameters of HL including GM (GM-HL) were 60-90 nm with a narrow range of the size distribution and the sizes were kept almost constant for over 4 weeks, suggesting that GM-HL could avoid the reticuloendothelial system in vivo. Furthermore, GM-HL accumulated more to the skeletal muscle cells of X chromosome-linked muscular distrophy (mdx) mice as compared to those of normal mice. Significantly, we succeeded in increasing dystrophin positive fibers in skeletal muscle cells of mdx mice using GM-HL along with the reduction of ototoxicity. It is suggested that GM should be carried more efficiently into the muscular cells of mdx mice by HL. These results indicate that HL could be an effective carrier in the DDS of GM therapy for DMD.
authors.affiliation: Division of Applied Life Science, Graduate School of Engineering, Sojo University, Kumamoto, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Yukihara
authors.forename: Kaori
authors.initials: K
authors.lastname: Ito
authors.forename: Osamu
authors.initials: O
authors.lastname: Tanoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Taku
authors.initials: T
authors.lastname: Matsushita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Masako
authors.initials: M
authors.lastname: Masuda
authors.forename: Shigemi
authors.initials: S
authors.lastname: Kimura
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ueoka
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008081:Liposomes; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*
chemical_list: D005839:Gentamicins; D008081:Liposomes