Facile In Situ Preparation and In Vitro Antibacterial Activity of PDMAEMA-Based Silver-Bearing Copolymer Micelles

Wenjing Lin,Kaihang Huang,Chufen Yang,Zilun Tang,Guobin Yi,Yunwei Huang,Yanzhe Li,Jinglian Lin,Yanlin Qin,Jufang Wang,Di Xiong,Jiabao Ling

doi:10.1186/s11671-019-3074-z

Abstract

Well-defined polymer micelles with core-shell structure are good delivery platform for stabilizing silver nanoparticles (AgNPs) in the field of antimicrobials targeting diseases. The rational construction of the polymer structure, an efficient, facile, and green preparation approach, and comprehensive exploration of the derived AgNPs are necessary, such as size, particle stability, antibacterial activity, and other properties. Herein, we designed and assessed the in vitro antimicrobial activity of AgNPs-decorated copolymer micelles with different copolymer topologies. First, linear or four-arm star triblock copolymers with the similar molecular weight and degree of polymerization were obtained, which consisted of DMAEMA for in situ reduction of silver ions to form AgNPs without external reducing agent. HEMA and PEGMA in micellar shell gave an enhanced stability of AgNPs during blood circulation. The combination of computational modeling and experimental results indicated that both types of micelles could fabricate AgNPs with monodisperse and spherical morphology. Star copolymer micelles stabilized AgNPs had smaller average size, better stability, and higher antibacterial activity than those with linear structure, which may due to higher stability of micelles from star copolymers. Furthermore, the cytotoxicity evaluation test showed that the achieved linear or star copolymers micelles stabilized AgNPs had good biocompatibility. This work provides a facile and universal approach in the rational design of micelles stabilized AgNPs with suitable topology for fighting against a wide range of bacterial infections.

Highlights

In the past few decades, a slate of traditional antimicrobial agents has been extensively used to treat infectious diseases
Synthesis and Characterization of Linear/Star Copolymers Linear copolymers PDMAEMA-b-PHEMA-b-PPEGMA and star copolymers (PDMAEMA-b-PHEMA-b-PPEGMA)4 were synthesized by ARGET ATRP polymerization of 2-(dimethylamino) ethyl methacrylate (DMAEMA), 2-hydroxyethyl methacrylate (HEMA), and PEGMA with Cupric bromide (CuBr2)/HMTETA as catalyst, Sn(Oct)2 as reducing agent, and EBiB or pentaerythritol which was previously acylated with BIBB as initiator in toluene (Scheme 2)
Polymeric micelles were self-assembled from PDMAEMAb-PHEMA-b-PPEGMA or (PDMAEMA-b-PHEMA-bPPEGMA)4 with the DMAEMA as the functional block, where the Ag+ ions were attracted and reduced into AgNPs without the participation of extra reducing agent

Summary

Introduction

In the past few decades, a slate of traditional antimicrobial agents has been extensively used to treat infectious diseases. Polymer matrix or external stabilizer is needed in order to stabilize the AgNPs. As known, polymer matrix is the most common method to solve the aggregation problem. Chemical reduction is a common and effective method. Silver nitrate is reduced into AgNPs by adding reductants such as hydrazine hydrate (N2H4), sodium borohydride (NaBH4), sodium citrate, and ascorbic acid in solution [20–23]. Hoda et al fabricated polystyrene-block-polyacrylicacid (PS-b-PAA) reverse micelles loaded with the 20 nm AgNPs under the influence of the reducing agent N2H4, and the PS blocks played the outer layer in toluene [24]. The above methods were not environment friendly, and the addition of excessive reductants produce by-products, making it difficult to purify AgNPs and restricting their application of antimicrobials targeting infectious diseases

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Results

Conclusion