Issue 13, 2020

Amphiphilic poly(esteracetal)s as dual pH- and enzyme-responsive micellar immunodrug delivery systems

Abstract

Poly(esteracetal)s are equipped with both acid-labile acetal and base-labile ester functionalities in their backbone, thus, providing dual pH-responsive degradation profiles. In this study, the cyclic esteracetal monomer 2-methyl-1,3-dioxan-4-one (MDO) was polymerised via a cationic ring-opening mechanism onto methoxy poly(ethylene glycol) (mPEG) affording amphiphilic mPEG-b-P(MDO) poly(esteracetal) block copolymers that self-assemble into well-defined monomodal micelles by direct hydration with aqueous buffers. Their pH-responsive behaviour towards rapid particle degradation was confirmed by DLS and 1H-NMR. Upon acidification or basification and lipase-mediated enzymatic hydrolysis, immediate polymer degradation and cargo release could be observed. As an example for further suitable applications, an amphiphilic immune stimulatory TLR-7 agonist (Adifectin) was co-formulated into mPEG-b-P(MDO) block copolymer micelles and its activity was investigated by TLR stimulation of RAW Blue macrophages. The degradable amphiphilic block copolymer was able to solubilize the drug more efficiently and retained its receptor activity. Consequently, mPEG-b-P(MDO) based amphiphilic poly(esteracetal)s can be considered as promising delivery systems for further immunodrugs and, thus, may contribute towards improving their translatability.

Graphical abstract: Amphiphilic poly(esteracetal)s as dual pH- and enzyme-responsive micellar immunodrug delivery systems

Supplementary files

Article information

Article type
Paper
Submitted
13 nov 2019
Accepted
25 fev 2020
First published
27 fev 2020
This article is Open Access
Creative Commons BY license

Polym. Chem., 2020,11, 2441-2456

Amphiphilic poly(esteracetal)s as dual pH- and enzyme-responsive micellar immunodrug delivery systems

L. Bixenmann, J. Stickdorn and L. Nuhn, Polym. Chem., 2020, 11, 2441 DOI: 10.1039/C9PY01716J

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