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Gel formulation containing mixed surfactant and lipids associating with carboplatin.

Abstract

The interaction of amphiphilic molecules such as lipids and surfactants with the hydrophilic drug carboplatin was investigated to identify suitable self-assembling components for a potential gel-based delivery formulation. (1) H-NMR Studies in sodium bis(2-ethylhexyl) sulfosuccinate (aerosol-OT, AOT)-based reverse micelles show that carboplatin associates and at least partially penetrates the surfactant interface. Langmuir monolayers formed by dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was found to also penetrate the more rigid monolayers containing cholesterol. A combined mixed surfactant gel formulation containing carboplatin and cholesterol for lymphatic tissue targeting was investigated for the intracavitary treatment of cancer. This formulation consists of a blend of the surfactants lecithin and AOT (1 : 3 ratio), an oil phase of isopropyl myristate, and an aqueous component. The phases of the system were defined within a pseudo-ternary phase diagram. At low oil content, this formulation produces a gel-like system over a wide range of H(2) O content. The carboplatin release from the formulation displays a prolonged discharge with a rate three to five times slower than that of the control. Rheological properties of the formulation exhibit pseudoplastic behavior. Microemulsion and Langmuir monolayer studies support the interactions between carboplatin and amphiphilic components used in this formulation. To target delivery of carboplatin, two formulations containing cholesterol were characterized. These two formulations with cholesterol showed that, although cholesterol does little to alter the phases in the pseudo-ternary system or to increase the initial release of the drug, it contributes significantly to the structure of the formulation under physiological temperature, as well as increases the rate of steady-state discharge of carboplatin.

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  • Publisher Full Text
  • Authors

    Woll KA, Schuchardt EJ, Willis CR, Ortengren CD, Hendricks N, Johnson M, Gaidamauskas E, Baruah B, Sostarecz AG, Worley DR, Osborne DW, Crans DC

    Institution

    Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.

    Source

    Chemistry & biodiversity 8:12 2011 Dec pg 2195-210

    MeSH

    1,2-Dipalmitoylphosphatidylcholine
    Antineoplastic Agents
    Carboplatin
    Cholesterol
    Delayed-Action Preparations
    Dioctyl Sulfosuccinic Acid
    Drug Carriers
    Drug Compounding
    Gels
    Hydrophobic and Hydrophilic Interactions
    Lecithins
    Lipids
    Magnetic Resonance Spectroscopy
    Micelles
    Microscopy, Polarization
    Molecular Structure
    Myristates
    Solubility
    Surface-Active Agents

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22162158