TY - JOUR

T1 - Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption

AU - Bøgh, Marie

AU - Baldursdóttir, Stefania G

AU - Müllertz, Anette

AU - Nielsen, Hanne M

N1 - Copyright © 2014. Published by Elsevier B.V.

PY - 2014/1/8

Y1 - 2014/1/8

N2 - Oral delivery of drugs, including peptide and protein therapeutics, can be impeded by the presence of the mucus surface-lining the intestinal epithelium. The aim of the present project was to design and characterize biosimilar mucus compatible with Caco-2 cell monolayers cultured in vitro to establish a more representative in vitro model for the intestinal mucosa. The rheological profile of a biosimilar mucus mixture composed of purified gastric mucin, lipids and protein in buffer was optimized by supplementing with an anionic polymer to display viscoelastic properties and a microstructure comparable to freshly isolated porcine intestinal mucus (PIM). Further, this multicomponent biosimilar mucus mixture was optimized with regards to the lipid content in order to obtain cellular biocompatibility with well-differentiated Caco-2 cell monolayers. In contrast, PIM was found to severely disrupt the Caco-2 cell monolayer. When combined with the Caco-2 cell monolayers, the final biosimilar mucus was found to significantly affect the permeability profiles for hydrophobic and hydrophilic small and large model drug compounds in different ways. In conclusion, the present study describes an improvement of the biorelevance of the Caco-2 cell culture model by application of mucus, resulting in an in vitro model of oral mucosa suitable for future assessment of innovative drug delivery approaches.

AB - Oral delivery of drugs, including peptide and protein therapeutics, can be impeded by the presence of the mucus surface-lining the intestinal epithelium. The aim of the present project was to design and characterize biosimilar mucus compatible with Caco-2 cell monolayers cultured in vitro to establish a more representative in vitro model for the intestinal mucosa. The rheological profile of a biosimilar mucus mixture composed of purified gastric mucin, lipids and protein in buffer was optimized by supplementing with an anionic polymer to display viscoelastic properties and a microstructure comparable to freshly isolated porcine intestinal mucus (PIM). Further, this multicomponent biosimilar mucus mixture was optimized with regards to the lipid content in order to obtain cellular biocompatibility with well-differentiated Caco-2 cell monolayers. In contrast, PIM was found to severely disrupt the Caco-2 cell monolayer. When combined with the Caco-2 cell monolayers, the final biosimilar mucus was found to significantly affect the permeability profiles for hydrophobic and hydrophilic small and large model drug compounds in different ways. In conclusion, the present study describes an improvement of the biorelevance of the Caco-2 cell culture model by application of mucus, resulting in an in vitro model of oral mucosa suitable for future assessment of innovative drug delivery approaches.

U2 - 10.1016/j.ejpb.2014.01.001

DO - 10.1016/j.ejpb.2014.01.001

M3 - Journal article

C2 - 24413146

VL - 87

SP - 227

EP - 235

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -