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. 2019 May 16;12(10):1610.
doi: 10.3390/ma12101610.

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

Wenzhao Jiang  1 , Jianwei Guo  2 , Weiqiu Wen  3 , Yong-Guang Jia  4 , Sa Liu  5
Affiliations

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

Wenzhao Jiang et al. Materials (Basel). .

Abstract

Polymeric nano-carriers are considered as promising tools in biomedical applications due to multiple attractive characteristics including their low toxicity, high loading capacity, controlled drug release capabilities, and highly tunable chemical properties. Here, a series of pH-sensitive star-shaped copolymers, Ad-P[(EMA-co-MAA)-b-PPEGMA]4, was prepared via electron transfer atom radical polymerization (ARGETE ATRP) and selective hydrolysis. These star-shaped copolymers can be self-assembled into micelles (Dh = 150-160 nm) and their critical micelle concentrations (CMC) were estimated to be 3.9-5.0 mg/L. The pH-sensitiveness of the micelles was evidenced by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The maximal paclitaxel (PTX) loading efficiency (DLC) and entrapment efficiency (EE) were 18.9% and 36%, respectively. In vitro release studies revealed that about 19% of the PTX released at an acidic condition of pH 1.2 over 70 h, whereas more than 70% was released within the same time interval at pH 6.8. In vitro cytotoxicity suggested that the low cytotoxicity of the blank micelles, while the PTX-loaded micelles providing the cytotoxicity close to that of free PTX. These results indicated that this novel pH-sensitive nano-carriers have great potential applications for oral drug-controlled release.

Keywords: adamantane; drug release; nano-carrier; pH-sensitive copolymer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Schematic formation of nano-carriers and the illustration of pH-dependent drug release.
Scheme 2
Scheme 2
Synthetic route of Ad-P[(EMA-co-MMA)-b-PPEGMA]4.
Figure 1
Figure 1
Proton nuclear magnetic resonance (1H NMR) spectra of Ad-P[(EMA-co-tBMA)]4 in CDCl3-d (a); Ad-P[(EMA-co-tBMA)-b-PPEGMA]4 in CDCl3-d (b); Ad-P[(EMA-co-MAA)-b-PPEGMA]4 in DMSO-d6 (c).
Figure 2
Figure 2
Critical micelle concentration (CMC) values of AdP-1 and AdP-2.
Figure 3
Figure 3
Titration curves (a); Effects of pH on Dh (b) and zeta potential (c) of the micelles formed by Ad-P1 and AdP-2.
Figure 3
Figure 3
Titration curves (a); Effects of pH on Dh (b) and zeta potential (c) of the micelles formed by Ad-P1 and AdP-2.
Figure 4
Figure 4
Transmission electron microscope (TEM) images of blank micelles formed by Ad-P1 at different pH conditions (a) pH = 2; (b) pH = 7.
Figure 5
Figure 5
1H NMR spectra of PTX-loaded micelles in CDCl3-d (a); PTX-loaded micelles in D2O (b).
Figure 6
Figure 6
TEM images of AdP-1 blank micelles (a), AdP-2 blank micelles (b), AdP-1 PTX-loaded micelles (c) and AdP-2 PTX-loaded miceles (d).
Figure 6
Figure 6
TEM images of AdP-1 blank micelles (a), AdP-2 blank micelles (b), AdP-1 PTX-loaded micelles (c) and AdP-2 PTX-loaded miceles (d).
Figure 7
Figure 7
In vitro release profiles of PTX-loaded micelles.
Figure 8
Figure 8
Cytotoxicity of blank and PTX-loaded micelles against 3T3 cells (a) and MCF-7 cells (b) for 48 h.
See this image and copyright information in PMC

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