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Examining the gastrointestinal transit of lipid-based liquid crystalline systems using whole-animal imaging

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Abstract

Lipid-based liquid crystalline (LC) systems have the potential to sustain the oral absorption of poorly water-soluble drugs in vivo, facilitating slow drug release from their complex internal structure. To further evaluate the dynamic relationship between gastric retention and sustained drug absorption for these systems, this study aimed to explore non-invasive X-ray micro-CT imaging as an approach to assess gastric retention. Pharmacokinetic studies were also conducted with cinnarizine-loaded LC formulations to correlate gastric retention of the formulation to drug absorption. The in vivo studies demonstrated the interplay between gastric retention and drug absorption based on the digestibility of the LC structures. An increase in non-digestible phytantriol (PHY) composition in the formulation relative to digestible glyceryl monooleate (GMO) increased the gastric retention, with 68 ± 4 % of formulation intensity remaining at 8 h for 85 % w/w PHY, and 26 ± 9 % for 60 % w/w PHY. Interestingly, it was found that PHY 30 % w/w in GMO provided the highest bioavailability for cinnarizine (CZ) amongst the other combinations, including GMO alone. The studies demonstrated that combining digestible and non-digestible lipids into LC systems allowed for an optimal balance between sustaining drug absorption whilst increasing plasma concentration (C max) over time, leading to enhanced oral bioavailability. The results demonstrate the potential for utilising non-invasive X-ray micro-CT imaging to dynamically assess the GI transit of orally administered liquid crystal-forming formulations.

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Acknowledgments

Funding is acknowledged from the Australian Research Council under the Discovery Projects scheme DP120104032. BJB is a recipient of an Australian Research Council Future Fellowship (FT120100697). We acknowledge Tanmay Joshi and Olga Gazukin for transmission electron microscopy (TEM) images, Bim Graham and Raymond Lam for GNP synthesis, Joanne Du and Linda Hong for SAXS analysis and Orlagh Feeney for assistance with UPLC. We also acknowledge the MBI Facility for provision of instrumentation, training and general support. SAXS measurements were performed on the SAXS/WAXS beamline at the Australian Synchrotron facility.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Drug Delivery Disposition and Dynamics - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia

    Anna C. Pham, Tri-Hung Nguyen & Ben J. Boyd

  2. Drug Discovery Biology - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia

    Cameron J. Nowell

  3. Medicinal Chemistry - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia

    Bim Graham

  4. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia

    Ben J. Boyd

Authors
  1. Anna C. Pham
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  2. Tri-Hung Nguyen
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  3. Cameron J. Nowell
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  4. Bim Graham
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  5. Ben J. Boyd
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Corresponding authors

Correspondence to Tri-Hung Nguyen or Ben J. Boyd.

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Pham, A.C., Nguyen, TH., Nowell, C.J. et al. Examining the gastrointestinal transit of lipid-based liquid crystalline systems using whole-animal imaging. Drug Deliv. and Transl. Res. 5, 566–574 (2015). https://doi.org/10.1007/s13346-015-0253-z

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