Tough robust dual responsive nanocomposite hydrogel as controlled drug delivery carrier of asprin

https://doi.org/10.1016/j.jmbbm.2019.01.017Get rights and content

Highlights

  • Dual responsive tough robust hydrogels also possess a fast recoverability.

  • Gold nanoparticles and clay acting as crosslinkers endow hydrogels with good biocompatibility.

  • Hydrogels exhibit controlled drug release property by adjusting the crucial influence factors.

Abstract

Smart mechanical strong hydrogels have gained increasing attention in the last decade. A novel tough robust biocompatible and dual pH- and temperature- responsive poly (N-isopropylacrylamide)/clay (Laponite XLS)/gold nanoparticles (Au-S-S NPs)/caboxymethyl chitosan (CMCTs) nanocomposite hydrogel was synthesized by a facile one-pot in situ free radical polymerization, using clay and Au-S-S NPs as the cross-linkers instead of toxic organic molecules. By tuning the crucial factors, concentration of Au-S-S NPs, CMCTs and clay, the obtained hydrogels exhibited the highest tensile stress of 535.5 kPa at the breaking deformation of 1579.5%. Furthermore, these synthesized hydrogels were tough enough and simultaneously owned a fast recoverability after unloaded in 15 min at room temperature. Moreover, effects of the above factors on swelling and swelling-shrinking behaviors of the prepared hydrogels were investigated in detail. In addition, these designed hydrogels also possessed a controlled drug release property of asprin by adjusting their inner crosslink density. Owing to this property, they could be used as the potential drug delivery carriers in future.

Graphical abstract

The synthesis process of PNIPAm/clay/Au-S-S/CMCTs semi-interpenetrated NC hydrogel.

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Introduction

Polymer hydrogels are cross-linked 3D hydrophilic networks comprising a great deal of water (Ye et al., 2016), which have drawn considerable attention in recent years in various fields involving food production, tissue engineering, medicine, soft devices, and so on. Smart hydrogels can evidently alter their volume or other properties in response to a variety of external stimuli, such as light (Li et al., 2017), temperature (Chen et al., 2015a), pH (Gao et al., 2015a), and magnetic/electric fields (Yang et al., 2015; Dai and Nelson, 2010). Thanks to the remarkable stimuli-responsive properties, smart hydrogels have been widely used in numerous applications such as intelligent sensors (Shi et al., 2015), tissue engineering scaffolds (Fan et al., 2016, Zhang et al., 2016), artificial cartilage (Hu et al., 2016), chemical valves actuators (Beebe et al., 2000), and drug delivery carriers (Chen et al., 2018), for most of which strong mechanical properties are needed. However, most of the conventional smart hydrogels generally have two critical defects: mechanical weak and brittle, and response to single stimuli, which seriously limits their high-end applications. Therefore, how to synthesize the dual/multi-stimuli hydrogels, with tough mechanical strong property, becomes one of the research hot-points in the last decade.

To address the first defect, plenty of strategies are proposed for preparing tough mechanical strong hydrogels, such as hydrophobically associated hydrogels (Insu et al., 2016), double network (DN) hydrogels (Chen et al., 2015), dual-crosslinked (DC) hydrogels (Cui et al., 2015), and nanocomposite (NC) hydrogels (Su and Chen, 2018). It is well known that the preparation of NC hydrogels is a simple efficient way to enhance the mechanical strength of the hydrogels, with the addition of reinforced nanofillers, such as carbon nanotubes, nanofibers, graphene oxide (GO) and clay nanosheets. Wang et al. (2012) have synthesized the poly(N-isopropylacrylamide) (PNIPAm)/Laponite XLS hydrogels, which have the highest breaking tensile strength about 380 kPa at corresponding failure strain of 960%. Hu et al. (2016) have fabricated the robust DC poly(acrylamide-co-acrylic acid) (PAm-co-Ac) NC hydrogels, using clay nanosheets and Fe3+ ions as the cross-linkers, which possess the highest tensile strength of 3.5 MPa at the breaking elongation of 2100%. Cui et al. (2015) have prepared the poly(acrylamide-co-stearyl methylacrylate) (PAm-co-SMA) DC NC hydrogels, using Laponite XLG and the hydrophobically associated interaction as the cross-linkers, which have a good mechanical property and a large deformation. All the NC hydrogels mentioned above have both good mechanical property and large deformation.

For the other defect, manufacturing the semi-interpenetration (semi-IPN) or interpenetration (IPN) networks is a direct method to synthesize the dual/multi-stimuli-responsive hydrogels. Chen et al. (2015b) have prepared the pH- and temperature- responsive semi-IPN poly (dimethylaminoethyl methacrylate) (PDMAEMA)/Laponite RD/carboxymethyl chitosan (CMCTs) NC hydrogel, which can be used as the drug delivery carriers. Shutong et al. (2015) have designed the pH/temperature responsive NC PNIPAm/chitosan/GO IPN hydrogels with the enhanced mechanical performance. Chen et al. (2018) have synthesized the mechanical strong dual responsive PNIPAm/Laponite XLG/CMCTs/genipin(GP) NC IPN hydrogels, which have the highest breaking tensile strength of 137.9 kPa at the failure strain of 446.1% and can be used as the drug release carriers of asprin. Ma et al. (2016) have fabricated novel multi-responsive anisotropic semi-IPN GO/PNIPAm/poly (methylacrylic acid) (PMMA) hydrogels, which own the light-, thermo-, pH- and ionic strength- sensitive properties. Among all the smart hydrogels, the pH- and temperature- responsive hydrogels are the widespread investigated hydrogels in the last decade. Moreover, N-isopropylacrylamide is the common raw material to synthesize the temperature-responsive hydrogels, and the polyelectrolyte materials (such as polyacrylate, chitosan, carboxymethyl chitosan and poly (ethylene imine)) are usually used to prepare pH- responsive hydrogels.

For the most physical cross-linked thermo-responsive NC PNIPAm/clay hydrogels, although they have high mechanical strength, simultaneously they also are unstable and have a bad recoverability. To overcome these defects, introducing the chemical cross-linked points into the hydrogels is an effective approach (Shi et al., 2015). Besides, incorporation of more coordination interaction groups (such as -COO-/Fe3+, H2PO4-/Fe3+, -SH/Au, etc.) into the networks, with the bond energy between non-covalent and covalent interaction, has become an effective method to further improve the toughness of the mechanical strong NC hydrogels (Peng et al., 2015, Meng et al., 2014, Qin et al., 2017). Based on the above description, we attempt to design a novel biocompatible much more tough mechanical strong pH- and temperature- responsive PNIPAm/CMCTs NC hydrogel with good fast recoverability through a simple one pot in situ free radical polymerization using clay (Laponite XLS) nanosheets and Au-S-S nanoparticles (NPs) as the cross-linkers instead of the common used toxic organic molecules. The optimum conditions for fabricating tough robust PNIPAm/clay/Au-S-S/CMCTs NC hydrogels was achieved by adjusting the crucial factors: the concentration of Au-S-S NPs, CMCTs and clay. What's more, the synthesized hydrogels also have a good biocompatibility (all the raw materials used possess good biocompatibility, which has been proved before (Qin et al., 2017; Agarwal et al., 2016; Zhang et al., 2013). In addition, for exploring the potential utilization as the drug delivery carriers, the drug absorbing and releasing tests of the synthesized hydrogels were conducted using acetylsalicylic acid (commonly known as Asprin) as the objective drug.

Section snippets

Materials

N-isopropylacrylamide (NIPAm, J&K Scientific Co., Ltd., China) was recrystallized from a toluene/n-hexane mixture and dried in vacuum at 40 ℃ before used. Synthetic hectorite clay of sol-forming grade Laponite XLS (Mg5.34Li0.66Si8O20(OH)4 Na0.66) was purchased from Rockwood Ltd., Germany, and used after dried in stove at 125 ℃ for 3 h. Carboxymethyl chitosan (CMCTs) (with the viscosity-average molecular weight of 361 kDa and substitution degree of 0.92) was prepared as mentioned in our previous

FTIR analysis

The FTIR spectra of clay, CMCTs, PcH, PcCH and PcNCH are shown in Fig. 2. As illustrated in Fig. 2a, there are two characteristic peaks appeared at 1635 and 1000 cm−1 in the FTIR curve of clay, corresponding to O-H deformation vibration of the absorbed water and Si-O stretching vibration, respectively (Chen et al., 2015b). In the spectrum of CMCTs, the peaks at 3450–3200 cm−1 are associated with both the O-H and N-H stretching vibrations, and the peak at 2900 cm−1 refers to the C-H stretching

Conclusion

In summary, we synthesized a novel tough robust biocompatible and dual pH- and temperature- responsive PNIPAm/clay/Au-S-S/CMCTs NC hydrogels in this paper through a one pot in situ free radical polymerization using Laponite XLS and Au-S-S NPs as the cross-linkers. By modulating the pivotal influence factors, the synthesized hydrogels displayed the highest tensile stress of 535.5 kPa at the breaking strain of 1579.5%. These hydrogels could dissipate a great deal of energy in the stretching

Acknowledgement

This work was financially supported by Shanghai International S&T Cooperation Fund (16160731302), National Natural Science Foundation of China (No. 51473031) and Natural Science Foundation of Shanghai (Grant no. 17ZR1401100).

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Author contributions

Y.C. and S.K. contributed equally.

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