Elsevier

Polymer

Volume 50, Issue 3, 28 January 2009, Pages 922-929
Polymer

Dual thermo-responsive and ion-recognizable monodisperse microspheres

https://doi.org/10.1016/j.polymer.2008.12.022Get rights and content

Abstract

A novel type of dual stimuli-responsive microspheres that simultaneously exhibit ion-recognition property based on the supramolecular host–guest complexation of crown ether receptors (benzo-18-crown-6-acrylamide) (BCAm) with specific ions and thermo-sensitivity based on the phase transition of poly(N-isopropylacrylamide) (PNIPAM) is fabricated in this study. The prepared poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)) microspheres are characterized by FT-IR spectroscopy, UV–vis absorption spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). SEM images and DLS data show that the synthesized microspheres exhibit nearly perfect spherical shape and high monodispersity. Moreover, according to the DLS results, P(NIPAM-co-BCAm) microspheres exhibit satisfactory thermo-responsive behavior and ion-recognition property. In K+ solutions, due to the formation of crown ether/K+ complexes, the LCST of P(NIPAM-co-BCAm) microspheres shifts to a higher temperature and the colloidal stability is increased. The P(NIPAM-co-BCAm) microspheres undergo a volume change from shrunken state to swollen network isothermally at a certain temperature by the addition of metal ions. Due to dual thermo-responsive and ion-recognition behaviors, this kind of microspheres would serve as promising candidates for sensors, controlled drug delivery systems and possibly new biomaterials.

Introduction

Stimuli-responsive “smart” microspheres are attracting increasing research interests due to their potential applications in biomedical and biotechnological fields [1], [2], [3]. Various external stimuli such as temperature [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], pH [14], [15], [16], [17], electric field [18], magnetic field [19], [20], [21], ionic strength [22], and light [23] may be used to induce drastic changes in physical–chemical properties and colloidal properties of these microspheres.

Poly(N-isopropylacrylamide) (PNIPAM) is one of the most widely studied temperature-responsive polymers, which exhibits a temperature-dependent phase transition in aqueous solution at a lower critical solution temperature (LCST) around 32 °C [24]. Since being reported by Pelton and Chibante for the first time in 1986 [25], thermo-sensitive PNIPAM microspheres have attracted extensive attention due to their theoretical importance and potential applications in many fields, such as controlled drug delivery systems [26], [27], biosensors [28], [29], enzyme and cell immobilizations [30], and microreactors [31]. As environmental temperature increases across the LCST, PNIPAM microspheres undergo a reversible volume change from swollen network to shrunken state and dramatically release free water at the same time.

Uniform particle size and shape are very important for stimuli-responsive microspheres to improve their performance in versatile applications, especially for drug delivery systems [32]. To that end, precipitation polymerization is an excellent technique which is able to prepare monodisperse microspheres without addition of any surfactant or stabilizer [33], [34], [35], [36]. PNIPAM-based microspheres with remarkably uniform size and shape can be readily prepared by precipitation polymerization in water at a temperature above the LCST of PNIPAM [37], [38].

The application of pure homopolymeric PNIPAM microspheres, however, is limited by their relatively fixed volume phase transition temperature and single thermo-sensitivity. For more favorable applications, such as drug delivery systems and chemical sensors, further functionalization of PNIPAM microspheres is needed. It is possible to increase the functionality of PNIPAM microspheres by copolymerizing with monomers that are sensitive to other stimuli [6], [39], [40]. Most reported multi-stimuli-responsive microspheres are dual thermo- and pH-responsive microspheres that are prepared by copolymerizing NIPAM with an ionizable monomer [27], [41], [42], [43]. Recently, dual photo- and thermo-responsive microgels were synthesized by incorporating functional dye or gold nanoparticles to convert light energy into heat [23], [44].

Sodium–potassium pump is a particularly important active transport system in biomembranes that maintains the homeostasis of life and normal metabolism [45], [46]. Normally, the concentration of potassium ions in the intracellular fluid is 140 mM, while extracellularly it is 5 mM. When the ATP–ADP energy transformation cycle is broken down, this high internal K+ concentration cannot be maintained through active transport and potassium ions release out from the cell, which results in the increase of local extracellular K+ concentration [47]. Thus, if the controlled-release kinetics of PNIPAM-based microspheres could respond to a specific ion signal (such as K+), such a smart system would serve as promising candidate for designing new drug delivery systems that release the drug in a controlled way to deliver the drug in the right place and at an adequate dosage guided by external ionic stimuli.

Crown ethers have remarkable properties of selectively recognizing specific ions and forming stable “host–guest” complexes. It has been reported that the copolymers of PNIPAM with pendant crown ether groups, poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)), have both thermo-sensitive and ion-recognition properties [48], [49], [50], [51], [52], [53], [54], [55]. When the BCAm receptors capture specific metal ions, the LCST of the copolymer shifts to a higher value. However, most of the investigated copolymers based on P(NIPAM-co-BCAm) were linear or linear-grafted types except our recently reported crosslinked P(NIPAM-co-BCAm) bulk hydrogel [56]. Monodisperse PNIPAM-based microspheres with crown ether receptors, which might be able to provide some unique functions for practical applications, have not been reported yet up to now.

In this study, we report on a novel kind of thermo-responsive microspheres possessing unique ion-recognition ability, which are monodisperse P(NIPAM-co-BCAm) microspheres prepared via precipitation copolymerization of NIPAM with BCAm. The chemical composition and microstructure of the prepared microspheres are characterized by FT-IR spectroscopy, UV–vis absorption spectroscopy and scanning electron microscopy (SEM), and the thermo-responsive behaviors and the isothermal swelling/deswelling behaviors triggered by ion-recognition are investigated by dynamic light scattering (DLS) technique.

Section snippets

Materials

N-Isopropylacrylamide (NIPAM, kindly provided by Kohjin Co., Ltd., Japan) is purified by recrystallization with a hexane/acetone mixture (50/50, v/v). Benzo-18-crown-6-acrylamide (BCAm) is synthesized according to reported procedures [57], [58]. N,N′-Methylenebisacrylamide (MBA, Chengdu Kelong Chemical Reagent Co.) is used as a crosslinker. 2,2′-Azobisisobutyronitrile (AIBN, Shanghai Reagent Fourth Factory) is recrystallized with ethanol and used as initiator. Tetrahydrofuran (THF) is freshly

Strategies for fabrication and ion-recognition function of the microspheres

The chemical structure and response mechanism of the proposed thermo-responsive and ion-recognition microspheres are schematically illustrated in Fig. 1. The thermo-responsive and ion-recognition microspheres are constructed from crosslinked P(NIPAM-co-BCAm) copolymers, in which PNIPAM acts as an actuator and the crown ether BCAm receptor acts as an ion-signal sensor. Crown ethers have remarkable properties of selectively recognizing specific ions and forming stable “host–guest” complexes. It

Conclusions

Monodisperse ion-recognizable P(NIPAM-co-BCAm) microspheres have been successfully fabricated via precipitation copolymerization of NIPAM with BCAm. In K+ solutions, the LCST of the P(NIPAM-co-BCAm) microsphere increases slightly. On the other hand, the formation of BCAm/K+ complexes in the outer layer of the P(NIPAM-co-BCAm) microspheres bring some charges onto the microsphere surfaces, which results in higher colloidal stability of the P(NIPAM-co-BCAm) microspheres in K+ solution than that of

Acknowledgments

This work has been supported by the National Natural Science Foundation of China (20674054), the Key Project of the Ministry of Education of China (106131), and Sichuan Youth Science and Technology Foundation for Distinguished Young Scholars (No. 08ZQ026-042). X.-J. Ju thanks the Student Innovation Foundation of Sichuan University (2006G007). The authors also wish to thank Ms. Xin-Yuan Zhang of Analytical and Testing Center at Sichuan University for her help in the SEM observation, and Kohjin

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