Acid-degradable poly(ortho ester urethanes) copolymers for potential drug carriers: Preparation, characterization, in vitro and in vivo evaluation

Herein, acid-degradable poly(ortho ester urethanes) (POEUs) were synthesized via polycondensation between an acid-labile ortho ester diamine and active esters of poly(ε-caprolactone) (PCL) diols with different molecular weights. The POEUs nanoparticles were easily fabricated using an oil-in-water em...

Full description

Saved in:
Bibliographic Details
Published in:Polymer (Guilford) 2017-04, Vol.114, p.1-14
Main Authors: Fu, Shengxiang, Yang, Guanqing, Wang, Jun, Wang, Xin, Cheng, Xu, Tang, Rupei
Format: Article
Language:English
Subjects:
Acids
Anticancer properties
Antitumor
Antitumor activity
Blood circulation
Cancer
Carbamate compounds
Chemical bonds
Degradation
Diols
Drug carriers
Drug delivery
Emulsion polymerization
Esters
Multicellular tumor spheroids
Nanoparticles
Ortho ester
pH effects
Polyurethane
Spheroids
Studies
Urethanes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Herein, acid-degradable poly(ortho ester urethanes) (POEUs) were synthesized via polycondensation between an acid-labile ortho ester diamine and active esters of poly(ε-caprolactone) (PCL) diols with different molecular weights. The POEUs nanoparticles were easily fabricated using an oil-in-water emulsion technique, whose ortho ester bonds in main-chains could be degraded at different rate in acidic pHs. DOX was loaded into the nanoparticles with high drug loading efficiency. In vitro release studies demonstrate that DOX is released in a pH-dependent manner. In vitro cellular uptake confirms that DOX-loaded POEUs nanoparticles can be more readily internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS), resulting in efficient antitumor efficiency of cancer cells. In vivo biodistribution and antitumor effect were evaluated by H22 tumor-bearing mice. The results demonstrate that DOX-loaded POEUs nanoparticles show a prolonged blood circulation time and improved accumulation in solid tumor, leading to enhanced therapeutic efficacy. [Display omitted] •POEUs were prepared via pH-sensitive ortho ester bridges with controlled hydrophobicity.•POEUs NPs have an accelerated degradation at pH 5.0 as a function of hydrophobicity.•These DOX-loaded NPs show an enhanced penetration and growth inhibition in MCTS.•DOX-loaded POEUs NPs show improved antitumor efficacy with lower toxicity in vivo.
ISSN:0032-3861
1873-2291
DOI:10.1016/j.polymer.2017.02.079