(163bj) Examination of the Effects of Poly(Ethylene Glycol) (Peg) Rich Matrices on the Transport of Multi Drug Resistance (Mdr) and Multi Drug Resistance Associated Protein (Mrp) Substrates Utilizing the Caco-2 Cell Model | AIChE

(163bj) Examination of the Effects of Poly(Ethylene Glycol) (Peg) Rich Matrices on the Transport of Multi Drug Resistance (Mdr) and Multi Drug Resistance Associated Protein (Mrp) Substrates Utilizing the Caco-2 Cell Model

Authors 

Santos-Roman, N. - Presenter, University of Puerto Rico - Mayaguez
Torres-Lugo, M. - Presenter, University of Puerto Rico, Mayaguez Campus
Licha, M. - Presenter, University of Puerto Rico - Mayaguez


Poly(ethylene glycol) (PEG) is a linear or branched neutral polymer that is widely used in a variety of biological applications for its unique properties. Recently, it has been observed that cells that have been in contact with lineal polyethylene glycol (PEG) exhibited an enhanced drug transport for known multi drug resistance associated protein (MRP) and multi drug resistance (MDR) substrates. Therefore, the main goal of this project is to investigate the effect of these hydrogels on the transport of known MDR and MRP substrates. Poly(ethylene glycol) hydrogels were synthesized via free radical polymerization using poly(ethylene glycol dimethacrylate N= 600, 1000) (PEGDMA) as the crosslinker and poly(ethylene glycol monomethacrylate N=200, 400, and 1000) as the backbone chain. The hydrogels were characterized by equilibrium swelling ratio, mesh size, partition coefficient, release of the model substrate fluorescein sodium salt, and caco-2 cytotoxicity. As expected slight effects of increasing tethered chain and/or crosslinker length showed an increase in swelling behavior. This correlates well with mesh size data that showed similar effects, although to a lesser extent. However, no effect of tethered chain was observed on partition coefficient. Release data indicated an anomalous behavior for most of the morphologies and relaxation-controlled release for the larger tethered chains. Two-hour cytotoxicy of microparticle suspensions dialyzed utilizing a 10^6 daltons dialysis membrane on Caco-2 cell model showed no cytotoxic effects. Finally, transport of fluorescein sodium salt (FLUO) trough Caco-2 cell model at 37 ºC shows an enhanced transport of FLUO as the tethered chain increases with a maximum observed at the intermediate length. At 4 ºC no polymer effect is observed, which suggests that the previous effects is due to active transport. Next steps include further investigation of the effects of PEG on the transport of MDR substrates and on membrane fluidity.