University of Hertfordshire

From the same journal

  • Aateka Patel
  • Arcadia Woods
  • Yanira Riffo-Vasquez
  • Anna Babin-Morgan
  • Marie-Christine Jones
  • Stuart Jones
  • Kavitha Sunassee
  • Stephen Clark
  • Rafael Torres Martin de Rosales
  • Clive Page
  • Domenico Spina
  • Ben Forbes
  • Lea Ann Dailey
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Original languageEnglish
Number of pages10
Pages (from-to)24-33
JournalJournal of Controlled Release
Journal publication date10 Aug 2016
Volume235
Early online date13 May 2016
DOIs
Publication statusPublished - 10 Aug 2016

Abstract

Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50 nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of 111In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p <0.001). When normalised to the delivered lung dose, the clearance kinetics of 111In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5 ± 0.9 h (R2 = 0.995) and 10.6 ± 0.3 h (R2 = 1.000) for healthy and inflamed lungs respectively (n = 3). In contrast, 111In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20 min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation.

ID: 17255631