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

Wenzhao Jiang,Jianwei Guo,Yong-Guang Jia,Sa Liu,Weiqiu Wen

doi:10.3390/ma12101610

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.

Highlights

Polymeric nano-carriers have been attracted considerable interest due to low toxicity, drug-controlled release abilities, high drug efficacy, et al [1,2,3,4,5,6,7,8].Especially, pH-sensitive nano-carriers have remarkable properties which enable them to bypass biological barriers and reach the goal of targeted drug delivery [9,10]
Such pH-sensitive properties can be used as oral drug delivery systems, where the drug could go through the acidic environment of stomach and be released upon increasing the pH
Ad-P[(EMA-co-MAA)-b-PPEGMA]4 was synthesized via ARGET ATRP and selective hydrolysis of tert-butyl groups of tert-butyl methacrylate (tBMA), as shown in Scheme 2

Summary

Introduction

PH-sensitive nano-carriers have remarkable properties which enable them to bypass biological barriers and reach the goal of targeted drug delivery [9,10]. The block PMAA of copolymers could keep tight in the protonated form under an acidic environment, whereas in the basic condition, the deprotonation and ionization of PMAA contribute to the swell of the blocks. Such pH-sensitive properties can be used as oral drug delivery systems, where the drug could go through the acidic environment of stomach and be released upon increasing the pH. Yang et al prepared a series of a linear amphiphilic copolymer containing a PMAA block for oral hydrophobic drug delivery [12,13,14]

Methods

Results

Conclusion