An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells MaƂgorzata I. Adamczak a, 1, * , Ellen Hagesaether b, 1 , Gro Smistad a , Marianne Hiorth a a Department of Pharmacy, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway b Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pilestredet 50, 0130 Oslo, Norway 1 These authors contributed equally * Corresponding author: e-mail address: m.i.adamczak@farmasi.uio.no, tel.: +47 22 85 65 98 Abstract Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate- coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell- irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the