Document Type

Article

Version Deposited

Accepted for publication (PostPrint)

Publication Date

3-24-2014

Publication Title

Journal of Biomaterials Science - Polymer Edition

DOI

10.1080/09205063.2013.870026

Abstract

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME-cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.

Comments

This is the accepted author manuscript from PubMed.

Published Citation

Brewer, E. & Lowman, A. (2014). Assessing the Transport of Receptor-Mediated Drug-Delivery Devices Across Cellular Monolayers, Journal of Biomaterials Science- Polymer Edition 25(5): 455-473.

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