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Human gastrointestinal drug delivery; an experimental chimeric approach
1Department of Cellular Physiology, Babraham Institute, Cambridge, UK.
Journal of Drug Targeting
|January 1, 1995
Summary
This study introduces a chimeric mouse model for human gastrointestinal drug delivery research. This model enables in vivo studies of human intestinal drug absorption, overcoming ethical limitations in human trials.
Area of Science:
- Pharmacology
- Gastroenterology
- Biomedical Engineering
Background:
- Human gastrointestinal drug delivery studies face ethical restrictions, limiting research.
- Developing alternative models is crucial for advancing drug delivery science.
Purpose of the Study:
- To establish and validate a chimeric mouse model for studying human gastrointestinal drug delivery.
- To investigate epithelial transcytosis of a model peptide across human small intestine in vivo using this model.
Main Methods:
- Subcutaneous transplantation of human intestine into severe combined immunodeficient (SCID) mice.
- Cultivation of human fetal intestine xenografts to achieve mature, functional tissue.
- In vivo assessment of horseradish peroxidase (HRP) transcytosis across the human intestinal epithelium.
Main Results:
- The chimeric mouse model successfully supported the differentiation of human fetal intestine into functional tissue resembling normal human gut.
- The model allowed for in vivo study of epithelial transcytosis of horseradish peroxidase, a model peptide.
Conclusions:
- The chimeric mouse model offers a viable and ethical alternative for studying human gastrointestinal drug delivery.
- This model provides essential basic scientific information relevant to human drug absorption and transport, overcoming interspecies extrapolation challenges.