Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 18 April 2018 / Approved: 18 April 2018 / Online: 18 April 2018 (16:28:21 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Polymers 2018, 10, 478
DOI: 10.3390/polym10050478

Abstract

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 kind 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, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 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 indicating that the transport pathways could undergo saturation.

Subject Areas

Chitosan-g-PMMA amphiphilic nanoparticles; thiolated polymers; mucoadhesion; mucosal drug delivery; Caco2 and HT29-MTX cell lines; apparent permeability in vitro.

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.