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Soheil Haddadzadegan, Farid Abedin Dorkoosh, Andreas Bernkop‐Schnürch
The oral administration of therapeutic peptides and proteins is favoured from a patient and commercial point of view. In order to reach the systemic circulation after oral administration, these drugs have to overcome numerous barriers including the enzymatic, sulfhydryl, mucus and epithelial barrier. The development of oral formulations for therapeutic peptides and proteins is therefore necessary. Among the most promising formulation approaches are lipid-based nanocarriers such as oil-in-water nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes and micelles. As the lipophilic character of therapeutic peptides and proteins can be tremendously increased such as by the formation of hydrophobic ion pairs (HIP) with hydrophobic counter ions, they can be incorporated in the lipophilic phase of these carriers. Since gastrointestinal (GI) peptidases as well as sulfhydryl compounds such as glutathione and dietary proteins are too hydrophilic to enter the lipophilic phase of these carriers, the incorporated therapeutic peptide or protein is protected towards enzymatic degradation as well as unintended thiol/disulfide exchange reactions. Stability of lipid-based nanocarriers towards lipases can be provided by the use to excipients that are not or just poorly degraded by these enzymes. Nanocarriers with a size <200 nm and a mucoinert surface such as PEG or zwitterionic surfaces exhibit high mucus permeating properties. Having reached the underlying absorption membrane, lipid-based nanocarriers enable paracellular and lymphatic drug uptake, induce endocytosis and transcytosis or simply fuse with the cell membrane releasing their payload into the systemic circulation. Numerous in vivo studies provide evidence for the potential of these delivery systems. Within this review we provide an overview about the different barriers for oral peptide and protein delivery, highlight the progress made on lipid-based nanocarriers in order to overcome them and discuss strengths and weaknesses of these delivery systems in comparison to other technologies.
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Haddadzadegan, S., Dorkoosh, F. A., & Bernkop‐Schnürch, A. (2022). Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers. Advanced Drug Delivery Reviews, 182, 114097. https://doi.org/10.1016/j.addr.2021.114097
Haddadzadegan, Soheil, et al. "Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers." Advanced Drug Delivery Reviews, vol. 182, 2022, pp. 114097, https://doi.org/10.1016/j.addr.2021.114097.
Haddadzadegan, Soheil, Farid Abedin Dorkoosh, and Andreas Bernkop‐Schnürch. "Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers." Advanced Drug Delivery Reviews 182 (2022): 114097. https://doi.org/10.1016/j.addr.2021.114097.
Haddadzadegan S., Dorkoosh F. A., Bernkop‐Schnürch A. Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers // Advanced Drug Delivery Reviews. — 2022. — Vol. 182. — P. 114097. — URL: https://doi.org/10.1016/j.addr.2021.114097
@article{haddadzadegan2022oral,
title = {{Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers}},
author = {Soheil Haddadzadegan and Farid Abedin Dorkoosh and Andreas Bernkop‐Schnürch},
journal = {Advanced Drug Delivery Reviews},
year = {2022},
volume = {182},
pages = {114097},
doi = {10.1016/j.addr.2021.114097},
url = {https://doi.org/10.1016/j.addr.2021.114097}
}TY - JOUR AU - Haddadzadegan, Soheil AU - Dorkoosh, Farid Abedin AU - Bernkop‐Schnürch, Andreas TI - Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers JO - Advanced Drug Delivery Reviews VL - 182 SP - 114097 PY - 2022 DA - 2022/01/06 DO - 10.1016/j.addr.2021.114097 UR - https://doi.org/10.1016/j.addr.2021.114097 ER -
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