Mucus permeating carriers: formulation and characterization of highly densely charged nanoparticles

The GI mucus layer represents a significant block to drug carriers absorption. Taking an example from nature, virus-mimicking nanoparticles (NPs) with highly densely charged surface were designed with the aim to improve their mucus permeation ability. NPs were formulated by combining chitosan with chondroitin sulfate and were characterized by particle size zeta-potential and hydrophobicity. The interaction occurring between NPs and diluted porcine intestinal mucus was investigated by a new method, Furthermore, the rotating tube technique was exploited to evaluate the NPs permeation ability in fresh undiluted porcine intestinal mucus. NPs (400-500 nm) presenting a slightly positive (4.02 mV) and slightly negative (-3.55 mV) zeta-potential resulted to be hydrophobic and hydrophilic, respectively. On the one hand the hydrophobic NPs undergo physico-chemical changes when incubated with mucus, namely the size increased and the zeta-potential decreased. On the other hand, the hydrophilic NPs did not significantly change size and net charge during incubation with mucus. Both types of NPs showed a 3-fold higher diffusion ability compared to the reference 50/50 DL-lactide/glycolide copolymer NPs (136 nm, 23 mV, hydrophilic). Based on these results, this work gives valuable information for the further design of mucus-penetrating NPs. (C) 2014 Elsevier B.V. All rights reserved.