Elsevier

Polymer

Volume 52, Issue 9, 19 April 2011, Pages 1917-1924
Polymer

Aqueous nanogels modified with cyclodextrin

https://doi.org/10.1016/j.polymer.2011.02.037Get rights and content

Abstract

In this work, the incorporation of reactive cyclodextrins (CDs) in aqueous nanogels based on poly(N-vinylcaprolactam) (VCL) is studied by surfactant-free precipitation polymerization process. α-, β-, γ-CDs were functionalized with acrylic groups and the average amount of vinyl bonds per CD molecule was adjusted to 2, 4, or 6. The increase of the CD concentration in the reaction mixture led to the reduction of the final hydrodynamic radius of nanogels from 227 nm to 62 nm. The increase of the vinyl groups number per CD molecule induced formation of smaller nanogels (Rh = 22.5 nm) and considerable increase of the crosslinking degree. Obtained cyclodextrin-modified nanogels show temperature sensitivity in aqueous medium with a volume transition point around 30 °C. The complexation properties of CDs incorporated in nanogel networks were proved by titration with phenolphthalein.

Introduction

In the recent years continued development of the creation of complex materials has been focused on the engineering over length-scales from molecular to the colloidal to the macroscopic in order to improve their properties for specific applications. Today’s efforts in nano- and micro-structured and multifunctional materials design focus on methods by which functional building blocks are assembled in complex architectures. Aqueous nano- and micro-gels are outstanding polymer materials because of their interesting properties such as small size, high porosity, large surface area, high chemical functionality, ability to swell in different solvents (e.g. water), and stimuli-sensitivity [1], [2]. Nano- and micro-gels can be used in colloidal form as microreactors [3], [4], drug carriers [5], [6], and antimicrobial agents but also as building blocks for design of colloidosomes [7], [8], hydrogels [9], [10], and films [11] targeting such applications as controlled release, tissue engineering and optics.

The chemical functionality of polymer nano- and micro-gels is extremely important for their application in different areas of science and technology. So far colloidal polymer networks have been modified by incorporation of ionizable or reactive groups [12], [13], [14], [15], integration of biomacromolecules [16], [17] or nanoparticles [18], [19].

In this context, cyclodextrins (CDs) are interesting functional units which can be integrated in polymer network of nano- and micro-gel colloids [20], [21]. Cyclodextrins are composed of α-1,4-coupled six, seven or eight d-glucose units which form cyclic oligomers. The caves of these host molecules have a diameter of 5–8 Ǻ and exhibit a hydrophobic internal cavity and a hydrophilic outer layer [22]. This structure and the hydrophobic cavity of CDs can act as host for various, suitable guest molecules. This unique property is commonly referred to as inclusion complex formation. The complexation leads to modification of the physical and chemical properties (solubility, smell, reactivity, etc.) of the guest molecules [23], [24].

So far, CDs were structurally incorporated in nanoparticles [25], polymers [26] or hydrogels [27], [28], [29], [30], [31], [32], [33] to modulate complexation and release of small molecules such as dyes or drugs. Alternatively, CDs were used for design of physically assembled polymer systems by formation of inclusion complexes between polymer-modified CDs and various guest molecule functionalized polymers. Widely used method for preparation of polymer networks containing CDs is the copolymerization of vinyl- or (meth)acryloyl-modified CDs with other vinyl monomers or macromonomers such as 2-hydroxyethyl methacrylate (HEMA) [27], [28], [29], N-isopropylacrylamide (NIPAm) [30], [31], acrylic acid (AA) [32], (meth)acrylated hyaluronic acid or poly(lactide) [33] or N-vinylpyrrolidone (NVP) [34]. Self-assembled polymer systems such as supramolecular hydrogels [35], [36], [37] and nano- and micro-particles [38], [39], [40] have been prepared based on host–guest CD inclusion complexes. Recently, the incorporation of CDs in aqueous colloidal nano- and micro-gels was reported. Microgels based on β-CD and poly(vinyl alcohol) (PVA) were prepared in inverse emulsion system by crosslinking of β-CD and PVA with epichlorhydrine. Alternatively, interpenetrating polymer network (IPN) microgels were synthesized by polymerizing methacrylic acid in β-CD/PVA microgels. It has been reported that the size of obtained microgel particles can be controlled by variation of stirring rate and emulsifier concentration between 50 μm and 200 μm [41].

The biodegradable polylactic acid-β-cyclodextrin (PLA-β-CD) crosslinked copolymer microgels were prepared by radical copolymerization of PLA macromonomer and polymerizable β-CD derivatives [42]. The β-CD derivatives with variable numbers of polymerizable vinyl groups were used in polymerization process. It has been shown that the hydrophilicity of the microgels increased with increasing β-CD contents, while the swelling ratios and degradation rate decreased.

The synthesis of aqueous microgels by precipitation polymerization of N-isopropylacrylamide (NIPAm) in presence of mono-vinyl substituted β-CD has been reported by Liu et al. [43]. β-CD/PNIPAm core–shell microgels were obtained by a two-stage precipitation polymerization in aqueous solution. At the first stage, core microgels with CD moieties were synthesized by precipitation copolymerization of NIPAm and mono-vinyl β-CD monomer with use of sodium-n-dodecylsulfate (SDS) as surfactant. At the second stage, using the core particles as seeds, PNIPAm shell was further prepared by NIPAm polymerization. The diameter of β-CD/PNIPAm core particles varied between 106 nm and 115 nm. It has been shown that with increase of β-CD content the temperature-induced deswelling of microgels decreases gradually.

Copolymer microgels were synthesized by surfactant-free precipitation copolymerization of N-vinylcaprolactam (VCL) with a mono-vinyl β-CD monomer in aqueous solutions [44]. It has been reported that addition of reactive CD could reduce the particle size and size distribution of the copolymer microgels. Obtained copolymer microgels exhibit thermally responsive changes of particle size in aqueous solutions, but similarly to PNIPAm system [43] the incorporation of the β-CD monomer into a PVCL microgel reduced its thermal sensitivity.

So far, the behavior of reactive cyclodextrins in precipitation polymerization was not investigated in details. Therefore, the primary aim of this study is the investigation of α-, β-, γ-CDs with different numbers of vinyl groups in precipitation polymerization process and their incorporation in nano- or micro-gel particles. For this study we selected vinylcaprolactam (VCL) as main monomer which has been already effectively used for synthesis of different microgel systems [45], [46], [47]. In this report we present the characterization of CD-modified nanogels with respect to their size, size distribution, swelling degree, and morphology. The accessibility of CD units in nanogel particles was evaluated by titration with model dyes.

Our first results indicate that it is possible to reduce the size of CD-modified colloidal networks down to 45 nm by keeping their most attractive properties such as temperature sensitivity, colloidal stability and narrow size distribution unaltered. We expect that cyclodextrin based nanogels provide useful functionalities such as effective bioconjugation, good adhesion to surfaces, controlled complexation and release of drugs, cosmetic ingredients, dyes or antimicrobial agents.

Section snippets

Materials

N-Vinylcaprolactam (VCL) was obtained from Aldrich and distilled by vacuum distillation. Acetoacetoxyethyl methacrylate (AAEM) was received from Aldrich and purified and destabilized by column chromatography over aluminum oxide; a further crosslinker N,N-methylene-bis-acrylamide (BIS) from Aldrich was used as received. The initiator, 2,2-azobis(2-methylpropionamidine) dihydrochloride (AMPA) from Aldrich was used without further purifications. α-, β-, γ-cyclodextrins (CD) produced by Wacker were

Results and discussion

A series of nanogels containing cyclodextrins (CD) were prepared by precipitation polymerization in aqueous phase. The modification of cyclodextrins with reactive vinyl groups was aimed to ensure fixation of CD in the nanogel network by formation of covalent bonds and effective incorporation in nanogels during radical polymerization process. Due to the fact that modified CDs used in the present study are functionalized with numerous acrylate groups, they can be considered as functional

Conclusion

Poly(N-vinylcaprolactam) nanogels functionalized with cyclodextrin units have been prepared by surfactant-free precipitation polymerization in water. We prepared series of α-, β-, γ-CDs functionalized with acrylic groups having the average amount of vinyl groups per CD molecule adjusted to 2, 4, or 6. Our experimental data indicate that the increase of the CD concentration in reaction mixture lead to reduction of the final hydrodynamic radius of nanogels from 227 nm to 62 nm. Increase of the

Acknowledgment

The authors thank VolkswagenStiftung for financial support of this research.

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