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In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: Effects of PEG chain length and PC incorporation

Authors

  • Beena Ashok,

    1. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612
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  • Lise Arleth,

    1. Manuel Lujan, Jr., Neutron Science Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545
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  • Rex P. Hjelm,

    1. Manuel Lujan, Jr., Neutron Science Center, Los Alamos National Laboratory, Los Alamos, New Mexico 87545
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  • Israel Rubinstein,

    1. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612
    2. Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612
    3. Jesse Brown VA Medical Center, Chicago, Illinois 60612
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  • Hayat Önyüksel

    Corresponding author
    1. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612
    2. Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60612
    • Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612. Telephone: 312-996-2097; Fax: 312-996-0098
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Abstract

Sterically stabilized micelles (SSM) composed of poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) and sterically stabilized mixed micelles (SSMM) composed of DSPE-PEG and egg-phosphatidyl choline (PC) have recently been introduced as novel lipid based carriers for water-insoluble drugs. However, factors that affect the solubilization behavior of these phospholipid micelles are not well understood. This study investigates the effect of PEG chain length and PC content on physical properties and solubilization potential of PEGylated phospholipid micelles. Critical micelle concentrations (CMC) determined for DSPE-PEG with different PEG chain lengths (2000, 3000, and 5000) using a fluorescent probe were in the micromolar range (0.5–1.5 μM) with higher CMC for longer PEG chain length. The size of micelles determined by quasi-elastic light scattering (QELS) showed that micellar systems became heterogeneous when PC was added at ≥25% for DSPE-PEG 2000 and ≥ 40% for DSPE-PEG 5000, respectively. Above these critical PC ratios a significant increase in aggregation number and formation of rodlike particles were observed by small angle neutron scattering (SANS). Solubilization of diazepam was greater with DSPE-PEG 2000 than DSPE-PEG 5000 simple micelles as determined by RP-HPLC. However, DSPE-PEG 5000 micelles showed greater improvement in solubilization of the water-insoluble drug with an increase in PC content. In conclusion, phospholipid micelle size and solubilization potential varied with PEG chain length and PC content in the mixed micelle. Aggregation number and shape of the micelles did not significantly change until the critical PC concentrations. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2476–2487, 2004

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