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Issue 23, 2019
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Intestine-penetrating, pH-sensitive and double-layered nanoparticles for oral delivery of doxorubicin with reduced toxicity

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Abstract

Herein, intestine-penetrating and pH-sensitive oral nanoparticles (NP2, ∼350 nm) with a double-layered structure have successfully been fabricated for enhanced oral delivery of doxorubicin with reduced systemic toxicity. Their core is composed of poly(ortho ester urethane) (POEU), which is biocompatible and acid-sensitive. Carboxymethyl chitosan (CMC) was used as the external coating layer, which effectively protected the nanoparticles in gastric fluid (pH 1.0). In addition, CMC-coated nanoparticles could promote penetration in the small intestine (pH 5.0–8.0) through tight-junction opening-mediated paracellular pathways, transcytosis, and lymphatic uptake of M cells. NP2 demonstrated good biocompatibility in vitro and in vivo. Doxorubicin-loaded NP2 (NP2/DOX) hardly released the loaded drug in the simulated gastric fluid (SGF), while 74.83% of DOX was released under mildly acidic conditions (pH 5.0). High bioavailability (75.4%) and reasonable drug distribution were achieved by passive targeting after oral administration of NP2/DOX. More importantly, continual NP2/DOX oral therapy could effectively inhibit the amplification of the H22 tumour without any noticeable systemic toxicity in vivo. These results demonstrated that NP2/DOX had great potential to overcome the obstacles of clinical oral delivery of DOX.

Graphical abstract: Intestine-penetrating, pH-sensitive and double-layered nanoparticles for oral delivery of doxorubicin with reduced toxicity

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Supplementary files

Article information


Submitted
30 Jan 2019
Accepted
30 Apr 2019
First published
02 May 2019

J. Mater. Chem. B, 2019,7, 3692-3703
Article type
Paper

Intestine-penetrating, pH-sensitive and double-layered nanoparticles for oral delivery of doxorubicin with reduced toxicity

M. Sun, D. Li, X. Wang, L. He, X. Lv, Y. Xu and R. Tang, J. Mater. Chem. B, 2019, 7, 3692
DOI: 10.1039/C9TB00212J

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