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Receptor-mediated peptide delivery in pulmonary epithelial monolayers
D Deshpande1, D Toledo-Velasquez, L Y Wang
1Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown 26506.
Pharmaceutical Research
|August 1, 1994
Summary
This study shows that linking transferrin (TF) to peptides enhances their uptake by lung cells via receptor-mediated endocytosis. Further treatment improved peptide transport across these cells.
Area of Science:
- Biotechnology
- Cell Biology
- Drug Delivery
Background:
- Pulmonary drug delivery faces challenges in efficiently reaching target cells.
- Receptor-mediated endocytosis offers a potential pathway for enhanced cellular uptake.
Purpose of the Study:
- To investigate the use of transferrin (TF) conjugation to enhance peptide delivery to the pulmonary epithelium via receptor-mediated endocytosis.
- To quantify the uptake and transport of a model peptide conjugated to TF.
Main Methods:
- Cultured rat alveolar epithelial cell monolayers were used to simulate the pulmonary epithelium.
- A molecular conjugate of transferrin (TF) and horseradish peroxidase (HRP) was synthesized using a disulfide linkage.
- Cellular uptake and transcellular transport of the conjugate were measured.
- Competition assays and brefeldin A (BFA) treatment were employed to study the endocytic pathway.
Main Results:
- Conjugation of HRP with TF significantly increased HRP uptake by alveolar cells in a concentration-dependent manner.
- Uptake was dependent on the transferrin moiety and specific to the TF receptor pathway.
- Internalization of the conjugate did not proportionally increase transcytosis, but BFA treatment enhanced it.
Conclusions:
- Transferrin-mediated endocytosis effectively enhances peptide uptake by pulmonary epithelial cells.
- Modulating intracellular transport pathways, such as with BFA, can further improve peptide transcytosis.
- This strategy holds promise for improving peptide-based pulmonary drug delivery.