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Development of 2D and 3D Mucus Models and Their Interactions with Mucus-Penetrating Paclitaxel-Loaded Lipid Nanocapsules

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Abstract

Purpose

To study, diffusion through mucus (3D model) of different formulations of paclitaxel loaded lipid nanocapsules (Ptx-LNCs), to interpret the results in the light of LNC behavior at air-mucus interface (2D model).

Methods

LNC surface properties were modified with chitosan or poly(ethylene glycol) (PEG) coatings of different size (PEG 2,000 to 5,000 Da) and surface charges. LNC diffusion through 446 μm pig intestinal mucus layer was studied using Transwell®. LNCs were spread at the air-water-mucus interface then interfacial pressure and area changes were monitored and the efficiency of triglyceride (TG) inclusion was determined.

Results

Ptx-LNCs of surface charges ranging from −35.7 to +25.3 mV were obtained with sizes between 56.2 and 75.1 nm. The diffusion of paclitaxel in mucus was improved after encapsulation in neutral or positively charged particles (p < 0.05 vs Taxol®). No significative difference was observed in the 2,000–5,000 PEG length for diffusion both on the 2D or 3D models. On 2D model positive or neutral LNCs interacted less with mucus. Highest efficiency of TG inclusion was observed for particles with smallest PEG length.

Conclusions

The results obtained with 2D and 3D model allowed us to select the best candidates for in vivo studies (neutral or positive LNCs with smaller PEG length).

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Authors and Affiliations

  1. INSERM U1066 MINT «Micro et nanomédecines biomimétiques», LUNAM Université, 49100, Angers, France

    Anne-Claire Groo, Jérôme Bejaud, Patrick Saulnier & Frederic Lagarce

  2. Ethypharm, Chemin de la poudrière, 76121, Grand-Quevilly, France

    Anne-Claire Groo & Caroline Ailhas

  3. Biophysical Chemistry Laboratory, Department of Physical Chemistry Faculty of Chemistry and Pharmacy, University of Sofia, J. Bourchier str. 1, 1164, Sofia, Bulgaria

    Kristina Mircheva, Ivan Panaiotov & Tzvetanka Ivanova

  4. Pharmacy Department, Angers University Hospital, Angers, France

    Frederic Lagarce

  5. INSERM U1066 MINT “Micro et nanomédecines biomimétiques » Bâtiment IBS-IRIS, LUNAM Université, 4 rue Larrey, 49933, Angers, France

    Frederic Lagarce

Authors
  1. Anne-Claire Groo
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  2. Kristina Mircheva
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  3. Jérôme Bejaud
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  4. Caroline Ailhas
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  5. Ivan Panaiotov
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  6. Patrick Saulnier
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  7. Tzvetanka Ivanova
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  8. Frederic Lagarce
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Corresponding author

Correspondence to Frederic Lagarce.

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Groo, AC., Mircheva, K., Bejaud, J. et al. Development of 2D and 3D Mucus Models and Their Interactions with Mucus-Penetrating Paclitaxel-Loaded Lipid Nanocapsules. Pharm Res 31, 1753–1765 (2014). https://doi.org/10.1007/s11095-013-1280-4

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  • DOI: https://doi.org/10.1007/s11095-013-1280-4

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