title: Therapeutic impact of erythropoietin-encapsulated liposomes targeted to bone marrow on renal anemia.
abstract: Bone marrow is a key element in the diagnosis of disorders of erythropoiesis, including anemia, and a potential target in their treatment. However, because efficient delivery of diagnostic and therapeutic agents to bone marrow is difficult, such delivery is achieved by administering drugs in large quantities that often have adverse effects. Here, we achieved selective delivery of recombinant human erythropoietin (rHuEPO) to bone marrow, via its encapsulation in liposomes with l-glutamic acid, N-(3-carboxy-1-oxopropyl)-, 1,5-dihexadecyl ester (SA) (liposome-EPO). The result, in a rabbit model of renal anemia, was a beneficial effect on hematopoiesis, better than with rHuEPO alone. Also, we determined that liposome-EPO delivery to bone marrow depended on specific uptake by bone marrow macrophages because of the presence of SA. These results indicate both that liposome-EPO is a new, promising erythropoietin-stimulating agent and that liposomes with SA have potential for diagnostic and therapeutic applications in diseases originating from bone marrow.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto 862-0973, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.forename: Keitaro
authors.initials: K
authors.lastname: Sou
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000740:Anemia / Q000188:drug therapy*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002478:Cells, Cultured; D004337:Drug Carriers; D016503:Drug Delivery Systems; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: bone marrow; erythropoietin; liposome; macrophages