Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption
[Display omitted] 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 i...
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| Published in: | European journal of pharmaceutics and biopharmaceutics Vol. 87; no. 2; pp. 227 - 235 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier B.V
01-07-2014
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| Abstract | [Display omitted]
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 regard to the lipid content in order to obtain cellular compatibility 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. |
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| AbstractList | 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 regard to the lipid content in order to obtain cellular compatibility 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. [Display omitted] 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 regard to the lipid content in order to obtain cellular compatibility 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. |
| Author | Müllertz, Anette Nielsen, Hanne M. Baldursdóttir, Stefania G. Boegh, Marie |
| Author_xml | – sequence: 1 givenname: Marie surname: Boegh fullname: Boegh, Marie – sequence: 2 givenname: Stefania G. surname: Baldursdóttir fullname: Baldursdóttir, Stefania G. – sequence: 3 givenname: Anette surname: Müllertz fullname: Müllertz, Anette – sequence: 4 givenname: Hanne M. surname: Nielsen fullname: Nielsen, Hanne M. email: hanne.morck@sund.ku.dk |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24413146$$D View this record in MEDLINE/PubMed |
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| Keywords | Viscoelasticity Mucosal drug delivery Biomacromolecular drug delivery Rheology Biosimilar mucus Biocompatibility Caco-2 cell culture Permeability Microstructure |
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Oral delivery of drugs, including peptide and protein therapeutics, can be impeded by the presence of the mucus surface-lining the intestinal... Oral delivery of drugs, including peptide and protein therapeutics, can be impeded by the presence of the mucus surface-lining the intestinal epithelium. The... |
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| SubjectTerms | Animals Biocompatibility Biomacromolecular drug delivery Biosimilar mucus Buffers Caco-2 cell culture Caco-2 Cells Gastric Mucins - chemistry Gastric Mucins - metabolism Humans Hydrophobic and Hydrophilic Interactions Intestinal Absorption Intestinal Mucosa - metabolism Lipids - chemistry Microstructure Mucosal drug delivery Mucus - chemistry Mucus - metabolism Permeability Pharmaceutical Preparations - chemistry Pharmaceutical Preparations - metabolism Proteins - chemistry Proteins - metabolism Rheology Swine Technology, Pharmaceutical - methods Time Factors Viscoelasticity |
| Title | Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption |
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