title: A drug formulation using an alginate hydrogel matrix for efficient oral delivery of the manganese porphyrin-based superoxide dismutase mimic.
abstract: In order for patients to avail of the therapeutic benefits of antioxidant drugs efficiently and conveniently, a robust oral delivery system needs to be developed. However, a common problem in oral drug delivery is ensuring that the drug remains functionally intact even after it has passed through the acidic environment of the gastrointestinal (GI) tract. To protect drugs within the GI environment, we formulated a design based on encapsulating liposomal drugs by using an alginate matrix as a carrier. The liposomal drug was composed of manganese porphyrin (Mn-por), which has been developed as a mimic of superoxide dismutase (SOD), as the therapeutic agent based on the antioxidative effect, namely superoxide (O2˙(-)) inhibitory activity. A cytochrome c assay revealed that the O2˙(-) inhibitory activity of Mn-por could be maintained even after treatment with simulated gastric and intestinal fluids. We demonstrated that oral administration of the formulated drug significantly inhibited the growth of transplanted tumors in mice. The drug formulation presented in this study would be a good candidate for orally available systems, which can effectively deliver SOD mimics.
authors.affiliation: Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. yuasa@rs.noda.tus.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Aikawa
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Yuasa
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008081:Liposomes; D008345:Manganese / Q000737:chemistry*; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000464:Alginates; D000975:Antioxidants; D006603:Hexuronic Acids; D008081:Liposomes; D008665:Metalloporphyrins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008345:Manganese; D020723:Glucuronic Acid; D013482:Superoxide Dismutase