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  • Title: Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration.
    Author: Nguyen TH, Hanley T, Porter CJ, Boyd BJ.
    Journal: J Control Release; 2011 Jul 30; 153(2):180-6. PubMed ID: 21497623.
    Abstract:
    This study is the first to demonstrate the ability of nanostructured liquid crystal particles to sustain the absorption of a poorly water soluble drug after oral administration. Cubic (V(2)) liquid crystalline nanostructured particles (cubosomes) formed from phytantriol (PHY) were shown to sustain the absorption of cinnarizine (CZ) beyond 48h after oral administration to rats. Plasma concentrations were sustained within the range of 21.5±1.5ng/mL from 12 to 48h. In stark contrast, cubosomes prepared using glyceryl monooleate (GMO) did not sustain the absorption of CZ and drug concentrations fell below quantifiable levels after 24h. Sustained absorption of CZ from PHY cubosomes lead to a significant enhancement (p<0.05) in oral bioavailability (F%=21%) compared to a CZ suspension (9%) and oleic acid emulsion (12%). Analysis of the nanostructured particles in simulated gastric and intestinal fluids using small angle x-ray scattering (SAXS) revealed that the V(2)Pn3m nanostructure of PHY cubosomes was maintained for extended periods of time, in contrast to GMO cubosomes where the V(2)Im3m nanostructure was lost within 18h after exposure, suggesting that degradation of the LC nanostructure may limit sustained drug release. In addition, PHY cubosomes were shown to be extensively retained in the stomach (>24h) leading to the conclusion that in the case of non-digestible PHY cubosomes, the stomach may act as a non-sink reservoir that facilitates the slow release of poorly water soluble drugs, highlighting the potential use of non-digestible LC nanostructured particles as novel sustained oral drug delivery systems.
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