Avtor/Urednik     Marušić, Maja; Zupančič, Tina; Hribar, Gorazd; Komel, Radovan; Anderluh, Gregor; Caserman, Simon
Naslov     #The #Caco-2 cell culture model enables sensitive detection of enhanced protein permeability in the presence of N-decyl-[beta]-d-maltopyranoside
Tip     članek
Leto izdaje     2013
ISSN     1871-6784 - New biotechnology
Jezik     eng
Abstrakt     Appropriate assessment of transepithelial permeability in vitro is needed to estimate and model trans-mucosal bioavailability to achieve oral delivery of protein biopharmaceuticals. The Caco-2 cell-based intestinal epithelium model is widely used for this purpose for low molecular mass drugs. The aim of this study was to test the suitability of the Caco-2 model for assessing enhanced transepithelial permeability to proteins. Four unrelated proteins were chosen to test the permeability of Caco-2 monolayers. It was found that proteins could cross the epithelium model, in spite of their size. All tested proteins had similar very low apparent permeability coefficients (Papp) of around 410-10cm/s. Protein stability over three-hour exposure to Caco-2 was also confirmed. Their crossing rate in a cell-free setup was also measured, to determine the upper limit of permeability to proteins. An epithelium permeability enhancer N-decyl--d-maltopyranoside (MP C10) was used to demonstrate accelerated permeability conditions. Papp values could be increased dose dependently up to about 110-7cm/s, close to the level in the cell-free setup, indicating distinctive potential of the model. This along with enhancing effect on known specific route permeators suggests involvement of the paracellular route in protein transport. Our results thus indicate that the Caco-2 model is a suitable tool for in vitro assessment of enhanced permeability to proteins.
Proste vsebinske oznake     Caco-2 cell culture model
detection of enhanced protein
technology
Caco-2 model celične kulture
detekcijo prepustnosti proteinov
tehnologija