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Article

Permeability of Novel Chitosan-g-Poly(Methyl Methacrylate) Amphiphilic Nanoparticles in a Model of Small Intestine In Vitro

Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 3200003 Haifa, Israel
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Polymers 2018, 10(5), 478; https://doi.org/10.3390/polym10050478
Received: 18 April 2018 / Revised: 22 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
(This article belongs to the Collection Polysaccharides)
Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized, for the first time, chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05–0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco-2 cells that mimic the intestinal epithelium and HT29-MTX cells that are a model of mucin-producing goblet cells. Then, we evaluated the effect of crosslinking, nanoparticle concentration, and thiolation on the permeability in vitro utilizing monolayers of (i) Caco-2 and (ii) Caco-2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco-2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp, suggesting that the transport pathways can undergo saturation. View Full-Text
Keywords: Chitosan-g-PMMA amphiphilic nanoparticles; thiolated polymers; mucoadhesion; mucosal drug delivery; Caco-2 and HT29-MTX cell lines; apparent permeability in vitro Chitosan-g-PMMA amphiphilic nanoparticles; thiolated polymers; mucoadhesion; mucosal drug delivery; Caco-2 and HT29-MTX cell lines; apparent permeability in vitro
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MDPI and ACS Style

Noi, I.; Schlachet, I.; Kumarasamy, M.; Sosnik, A. Permeability of Novel Chitosan-g-Poly(Methyl Methacrylate) Amphiphilic Nanoparticles in a Model of Small Intestine In Vitro. Polymers 2018, 10, 478. https://doi.org/10.3390/polym10050478

AMA Style

Noi I, Schlachet I, Kumarasamy M, Sosnik A. Permeability of Novel Chitosan-g-Poly(Methyl Methacrylate) Amphiphilic Nanoparticles in a Model of Small Intestine In Vitro. Polymers. 2018; 10(5):478. https://doi.org/10.3390/polym10050478

Chicago/Turabian Style

Noi, Imrit; Schlachet, Inbar; Kumarasamy, Murali; Sosnik, Alejandro. 2018. "Permeability of Novel Chitosan-g-Poly(Methyl Methacrylate) Amphiphilic Nanoparticles in a Model of Small Intestine In Vitro" Polymers 10, no. 5: 478. https://doi.org/10.3390/polym10050478

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