Journal of Controlled Release 75 (2001) 167–172 www.elsevier.com / locate / jconrel The preparation of the chronic hyper-endotoxemia experimental animal model by means of a drug delivery system a a a, a * Sachiro Kakinoki , Kouji Yukutake , Isao Kaetsu , Kumao Uchida , a b b b b Kouichi Sutani , Takuya Kosumi , Norio Usui , Takeo Yonekura , Akio Kubota , b Harumasa Ohyanagi a Interdisciplinary Graduate School of Science and Technology, Kinki University, Higashi, Japan b Department of Surgery II, Kinki University School of Medicine, Higashi, Japan Received 31 January 2001; accepted 9 May 2001 Abstract A drug delivery system (DDS) consisting of lipopolysaccharide (LPS) as a drug and 2-hydroxyethyl methacrylate (HEMA)-diethylene glycol dimethacrylate (2G) or –polyethylene glycol dimethacrylate (4G, 9G) copolymer was prepared, and used for the efficient preparation of an experimental animal model of chronic hyper-endotoxemia. The release profiles of LPS in the in-vitro test were greatly influenced by the composition of HEMA-2G, 4G, 9G in the copolymer. It was found that LPS release from the DDS continued gradually and constantly throughout 2 weeks. In the in-vivo experiment with rats, the DDS maintained a high blood concentration level of LPS for 3 days. These results strongly suggest the possibility of convenient and reproducible preparation of a chronic hyper-endotoxemia animal model.  2001 Elsevier Science B.V. All rights reserved. Keywords: Drug delivery system (DDS); Controlled release; 2-Hydroxyethyl methacrylate copolymer; Chronic hyper-endotoxemia experimental animal model; Lipopolysaccharide 1. Introduction on pathological clarification is urgently required. For this purpose, the preparation of a disease animal It is known that chronic hyper-endotoxemia model is necessary. Research on chronic hyper-endo- caused by gram-negative bacteria infection [1] after toxemia model using disease promoting substances trauma damage or surgery might further cause and small animals has been reported by many multiple organ dysfunction syndrome. However, this authors [2,3]. However, a method of convenient and has not yet been clarified. A therapeutic study based reproducible preparation of an animal model has not been established satisfactorily. Lipopolysaccaride (LPS) is the carrier of gram- *Corresponding author. Present address: Department of Nu- negative bacteria and consists of lipid A, core clear-Reactor Engineering, Faculty of Science and Technology, polysaccharide and O antigen polysaccharide, which Kinki University, Kowakae 3-4-1, Higashi-Osaka, 577-8502 are combined by covalent binding. Small doses of Japan. Tel.: 181-6-6730-5880, ext. 4373; fax: 181-6-6723-2721. E-mail address: kaetsu@ned.kindai.ac.jp (I. Kaetsu). LPS cannot prevent gram-negative sepsis, while 0168-3659 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0168-3659(01)00388-1