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

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• 作者：Irene Pereira de Sousa^a ; Corinna Steiner^a ; Matthias Schmutzler^b ; Matthew D. Wilcox^c ; Gert J. Veldhuis^d ; Jeffrey P. Pearson^c ; Christian W. Huck^b ; Willi Salvenmoser^e ; Andreas Bernkop-Schnü ; rch^a ; ^{Andreas.Bernkop@uibk.ac.at" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Mucus-penetrating particles ; Diffusion ; Mucus ; Hydrophobicity ; Chitosan ; Chondroitin sulfate
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：97
• 期：part_PA
• 页码：273-279
• 全文大小：911 K

文摘

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, ζ-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) ζ-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 ζ-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.