Engineering Elastin-like Polypeptides for Polyphenol Capture and Permeation through an in Vitro Nasal Mucosa Barrier
Abstract
Intranasal (IN) administration provides a potential drug delivery route to the brain without passing the blood-brain barrier, allowing for the delivery of larger therapeutics for diseases such as Alzheimer's disease (AD). However, effective IN administration is compromised by mucociliary clearance (MCC) and the use of complex formulations of thermo-gelling modalities to reduce MCC. This study uses biomimetic elastin-like polypeptides (ELPs) to gel at nasal passage temperatures, capture an AD-relevant polyphenol, vescalagin (VSG), and deliver VSG through a nasal mucosa model. First, a library of ELPs was produced bearing either tyrosine, phenylalanine, serine, or leucine guest residues. The phenyl-bearing ELPs elicit a physiologically relevant gelation temperature and have the best VSG drug binding, as determined by a pull-down assay. Next, a di-block ELP was produced with a tyrosine-bearing block for drug binding and phase separation and a leucine-bearing block that remains soluble and presents a polyarginine tag (10xR) for cell interaction. While the di-block ELP resulted in stable microgels compared to mono-block ELPs upon phase separation, adding the 10xR tag mitigated this stability, returning the di-block ELP to coalescence behavior. However, the 10xR tag elicited ELP interaction with RPMI cells, enhanced VSG accumulation at the cell-mucous surface of an in vitro nasal mucosa model, and increased VSG permeation compared to un-tagged ELP or VSG alone. Future work can use these findings to improve ELP design for IN applications and investigate in vivo efficacy.
Recommended Citation
D. W. Nelson et al., "Engineering Elastin-like Polypeptides for Polyphenol Capture and Permeation through an in Vitro Nasal Mucosa Barrier," Journal of Drug Delivery Science and Technology, vol. 111, article no. 107119, Elsevier, Sep 2025.
The definitive version is available at https://doi.org/10.1016/j.jddst.2025.107119
Department(s)
Chemical and Biochemical Engineering
Keywords and Phrases
Drug toxicity; Elastin-like polypeptides; Intranasal drug delivery; Polyphenol therapeutics; RPMI nasal mucosa model; Vescalagin
International Standard Serial Number (ISSN)
1773-2247
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2025 Elsevier, All rights reserved.
Publication Date
01 Sep 2025
Comments
National Institutes of Health, Grant I01RX003502