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Sterically Stabilized Phospholipid Mixed Micelles: In Vitro Evaluation as a Novel Carrier for Water-Insoluble Drugs

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Abstract

Purpose. Sterically stabilized phospholipid micelles (SSMs) composed of poly(ethylene glycol-2000)-grafted distearoyl phosphatidylethanolamine (PEG(2000)-DSPE) are new and promising lipid-based carriers for water-insoluble drugs. This study investigates and compares sterically stabilized mixed micelles (SSMM), composed of (PEG(2000)-DSPE) plus egg-phosphatidylcholine, with SSM as a novel delivery system for improved solubilization of water-insoluble drugs using paclitaxel as a model.

Methods. Paclitaxel was solubilized in SSM (P-SSM) and SSMM (P-SSMM) by coprecipitation and rehydration with isotonic 0.01M HEPES buffer, pH 7.4. After separation of excess drug by centrifugation, mean particle size and morphology of particles in the supernatant were determined by quasi-elastic light scattering and transmission electron microscopy. The solubilization potentials of SSMM and SSM for paclitaxel were determined by reverse phase high pressure liquid chromatography (RP-HPLC). Cytotoxic activity of paclitaxel in SSMM, SSM, and dimethyl sulfoxide (10% DMSO) was determined against human breast cancer cells (MCF-7).

Results. Mean hydrodynamic diameter of P-SSMM and P-SSM were 13.1 ± 1.1 nm and 15 ± 1 nm (n = 3), respectively. SSMM solubilized 1.5 times more paclitaxel than SSM for the same total lipid concentration. Solubilized paclitaxel amount increased linearly with an increase in lipid concentration. A therapeutically relevant lipid concentration (15 mM) of SSMM solubilized 1321 ± 48μg/ml of paclitaxel. Paclitaxel in the absence of sufficient SSM aggregated to form lipid-coated crystals. P-SSMM, P-SSM, and paclitaxel in DMSO had comparable cytotoxic activities against MCF-7 cells.

Conclusions. SSMM showed increased solubilization potential compared with SSM while retaining all of its own advantages. Therefore, it can be used as an improved lipid-based carrier for water-insoluble drugs.

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Authors and Affiliations

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

    Aparna Krishnadas, Israel Rubinstein & Hayat Önyüksel

  2. West Side Division, Chicago VA Health Care System, Chicago, Illinois, 60612

    Israel Rubinstein

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  1. Aparna Krishnadas
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  2. Israel Rubinstein
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  3. Hayat Önyüksel
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Correspondence to Hayat Önyüksel.

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Krishnadas, A., Rubinstein, I. & Önyüksel, H. Sterically Stabilized Phospholipid Mixed Micelles: In Vitro Evaluation as a Novel Carrier for Water-Insoluble Drugs. Pharm Res 20, 297–302 (2003). https://doi.org/10.1023/A:1022243709003

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