Preparation of Liposomes Modified with Lipopeptides Using a Supercritical Carbon Dioxide Reverse-phase Evaporation Method

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  • Aburai Kenichi
    Department of Pure and Applied Chemistry, Tokyo University of Science
  • Yagi Nobuhiro
    Department of Pharmaceutical Sciences, Toho University
  • Yokoyama Yuusaku
    Department of Pharmaceutical Sciences, Toho University
  • Okuno Hiroaki
    Department of Pharmaceutical Sciences, Toho University
  • Sakai Kenichi
    Department of Pure and Applied Chemistry, Tokyo University of Science
  • Sakai Hideki
    Department of Pure and Applied Chemistry, Tokyo University of Science
  • Sakamoto Kazutami
    Department of Pure and Applied Chemistry, Tokyo University of Science
  • Abe Masahiko
    Department of Pure and Applied Chemistry, Tokyo University of Science

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Although liposomes are considered to be one of the most promising carriers for drug delivery systems (DDS), they have drawbacks such as insufficient drug-entrapment efficiency and long-term stability. The objectives of this study are to improve the trapping efficiency by addition of lipopeptides (LPs), and using a supercritical CO2 reverse-phase evaporation (SCRPE) process, along with incorporation of PEG-modified phospholipids to improve long-term stability. In this study, bovine serum albumin (BSA) was used as a model drug substance for entrapment by liposomes.<br>Improvements in the entrapment efficiency and stability of liposomes were achieved by modification with LPs and use of a SCRPE preparation process. The BSA-entrapment efficiency of liposomes modified with cationic LPs with arginine residues, as a result of their ionic interactions, was six times that of liposomes prepared by the Bangham method. Use of a SCRPE method along with LP modification further enhanced entrapment and enabled spontaneous formation of unilamellar liposomes with long-term stability. Liposomes consisting of DPPC/Chol/C16-Arg2/DSPE-PEG2000 (60/30/5/5), with up to 70% entrapment efficiency for BSA and a stability level of 90% for over 40 h, were obtained. DSC and SAXS analyses indicated that certain amounts of LP in the DPPC induced phase-transitional and structural changes in the lamellar membrane, and these changes improved the DDS carrier properties.<br>The SCRPE method provides organic-solvent-free liposomes, and the LPs for the liposome modification are derivatives of amino acids and fatty acids, which are sustainable and biocompatible materials. This study therefore suggests that there are opportunities for the development of novel DDS carriers with excellent performance and which address environmental concerns.

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