54 research outputs found

    Pressure Induced Topological Phase Transitions in Membranes

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    Some highly unusual features of a lipid-water liquid crystal are revealed by high pressure x-ray diffraction, light scattering and dilatometric studies of the lamellar (bilayer LαL_{\alpha}) to nonlamellar inverse hexagonal (HIIH_{II}) phase transition. (i) The size of the unit cell of the HIIH_{II} phase increases with increasing pressure. (ii) The transition volume, ΔVbh\Delta V_{bh}, decreases and appears to vanish as the pressure is increased. (iii) The intensity of scattered light increases as ΔVbh\Delta V_{bh} decreases. Data are presented which suggest that this increase is due to the formation of an intermediate cubic phase, as predicted by recent theoretical suggestions of the underlying universal phase sequence.Comment: 12 pages, typed using REVTEX 2.

    A Dicarboxylic Fatty Acid Derivative of Paclitaxel for Albumin-Assisted Drug Delivery

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    Paclitaxel is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize paclitaxel (PTX) by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3-pentadecylglutaric (PDG) acid which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (~5% over 72 h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor bearing mice, [3H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 hours. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23-h half-life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics
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