[Antioxidant and anticancer properties of metalloporphyrins embedded in liposomes].
Reactive oxygen species (ROS) are implicated in many disease such as inflammation, arteriosclerosis, cancer. Therefore, a water-soluble cationic metalloporphyrins with SOD activity are studied widely as antioxidant drugs. Further, liposomes are applied to drug delivery system (DDS) as drug carriers and investigated for example disposition and stability. We designed PEG modified liposomes for avoiding reticuloendothelial system (RES) and embedded cationic metalloporphyrins for DDS, evaluated antioxidant and anticancer property. Preservation of these particle size measured DLS in an in vitro system, in order to simulate in vivo conditions of flow. Result of this measurement, we found Pluronic F-68/ liposomes have a long circulation property, and avoid fusion with plasma protein. SOD activity was determined by the stopped-flow analysis and cytochrome c assay, which allowed the evaluation of k(cat) and IC(50) for the reaction with a superoxide anion radical (.O(2)(-)). Anti cancer property was measured by cell viability test. We found that F-68/ liposomes were the most effective catalyst as antioxidant and anticancer. These results revealed that porphyrin-embedded PEG-liposomes had the property of long circulation in blood and that this compound was effective as a SOD model compound with a drug carrier capacity.
Yuasa
Makoto
M
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan. yuasa@rs.noda.tus.ac.jp
Oyaizu
Kenichi
K
Murata
Hidenori
H
Sahara
Yoshizumi
Y
Hatsugai
Tomomi
T
Ogata
Akihiko
A
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer; D013482:Superoxide Dismutase / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D008081:Liposomes; D008665:Metalloporphyrins; D020442:Poloxamer; D013481:Superoxides; D045304:Cytochromes c; D013482:Superoxide Dismutase