| Budget Amount *help |
¥9,100,000 (Direct Cost: ¥9,100,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Research Abstract |
In present study, the knowledge accumulated by development of an artificial red blood cell or artificial platelets is exploited. We incorporated the recognition sites, which were made of ligands such as receptor proteins and peptides or sugar chains, into the surface of these nano-particles by a simple method, aiming to making it intelligent and effective in a medical treatment. In 2003, we synthesized the large amount of the amino acid-type lipids with two chains, and examined the conjugation method of these lipids to oligopeptides or oligosaccharides by a solid-phase synthesis method. Then, we obtained the polyethyleneglycol-lipids with two or four alkyl chains. Furthermore, the functional PEG-lipid was synthesized in a large scale from a-maleimide, ω-succinimide PEG. Moreover, we also synthesized the functional PEG-lipids by coupling the alkyl chains in the disulfides bond as being considered as the membrane expanding packing, and combined maleimide PEG at the terminal. Next, for th
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e liposomes contaminated with lipopolysaccharide(LPS) as a bioactive substance, a surfactant treatment was applied to quantitatively measure the LPS content by using the interfacial transfer phenomenon. In 2004, the maleimide PEG lipid was introduced on the liposome surface by the interfacial transfer method. Then, proteins of which molecular weight was different (Lactalbumin(Mw : 14kDa), rHSA (66.5kDa), IgG (150kDa), Ferritin (460kDa), and Thyrogrobulin (670kDa)) were combined to the PEG lipid and the rate of the resulting protein-lipids isolated from the liposome surface (interfacial transfer) was analyzed. As a result, good correlation was acquired between the number and length of the alkyl chains of the PEG lipid, and the protein molecular weight. Moreover, if a recognition molecule (saccharide or oligopeptide) is conjugated on the liposome surface and then modified with PEG chains, the recognition ability is considered to be masked with the PEG chain. However, it was clarified that functional expression was switched when PEG lipids was isolated from the surface (interfacial transfer). From the above results, the novel drug carriers which can control pharmacokinetic can be designed by utilizing the isolation phenomenon of the PEG-lipids or protein-conjugated PEG-lipids modifying the liposome surface. Less
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