Structural, thermal, mechanical, swelling, drug release, antibacterial and cytotoxic properties of P(HEA/IA)/PVP semi-IPN hydrogels

https://doi.org/10.1016/j.cherd.2017.03.030Get rights and content

Highlights

  • Synthesis of novel hydrogels by the free-radical crosslinking polymerization based on HEA, IA and PVP.

  • Hydrogels with pH and temperature sensitivity.

  • Controlled release of vitamin B3, in form nicotinamide.

  • Short-term antibacterial examination and satisfied cytocompatible properties of P(HEA/IA)/PVP samples.

Abstract

The aim of this work was to synthesize a series of semi-interpenetrating polymer networks (semi-IPNs) of 2-hydroxyethyl acrylate and itaconic acid, in the presence of poly(N-vinylpyrrolidone). Samples were synthesized by free radical copolymerization with constant PVP and variable IA content and characterized for structural, morphological, thermal, swelling, drug release, antibacterial and cytotoxic properties. The chemical structure of samples was confirmed by Fourier-transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) was used to examine morphology of samples and glass transition temperatures were determined by differential scanning calorimetry (DCS). The pH and temperature sensitivity was confirmed by measuring the dependence of the degree of swelling on pH and temperature. All samples show volume phase transition temperature (VPTT) around 47 °C. Drug release profiles were investigated using vitamin B3 as a model drug. The vitamin B3 transport mechanism was studied by fitting experimental data to five different model equations and calculating the corresponding parameters. It was also observed that IA content has a marked influence on the release profiles of vitamin B3, so the rate of drug release can be designed by changing the HEA/IA ratio. Cell viability, performed using MTT test, was high for all samples and all concentration of extract used. The antibacterial activity of hydrogels was determined against Pseudomonas aeruginosa. It turns out that IA content and time of exposure have an influence on the antibacterial potential. All samples showed satisfied cell viability. Due to these characteristics, P(HEA/IA)/PVP semi-IPNs represent interesting biomaterials for biomedical applications.

Introduction

Synthetic hydrogels have well definied structure which can be modified in order to achieve the desired properties. The convenient method to modify the properties of hydrogels is to prepare multi-component polymer materials. The technique of preparing semi-interpenetrating polymer networks, as multi-component materials, is frequently used in the design and synthesis of various hydrogels. Semi-IPN is a blend of two polymers where only one is crosslinked in the presence of a linear polymer. These networks, in most cases show physico-chemical properties that can remarkably differ from those of their macromolecular constituents. Due to the outstanding performances of such materials semi-IPNs have been applied in many areas including medicine and pharmacy (Das, 2013, Roland, 2013, Wang et al., 2011).

Poly(2-hydroxyethyl acrylate) (PHEA) is one of the commonly used polymers for the synthesis of hydrogels, due to its biocompatibility and high hydrophilicity. PHEA hydrogels found a lot of applications in pharmaceutical and biomedical fields. It can be used for biomaterials as coatings, intraocular lenses, tissue scaffolds and devices for controlled drug delivery. To improve mechanical stability or swelling properties of hydrogels based on PHEA, they can be combined with hydrophilic polymers into blends or semi IPNs (Baino, 2010, Sanna et al., 2012, Chen et al., 2007).

Poly(vinyl pyrrolidone) (PVP), water soluble synthetic polymer, is widely used in medical applications, such as a blood plasma extender, and a carrier for drug delivery. PVP has low toxicity and it is used in medical, food, cosmetics and as a film-forming agent. Because of its special molecular structure, PVP has many outstanding properties. PVP has satisfied biocompatibility and hydrophilic properties, which have been used for composite tissue engineering matrices. It is one of the most frequently used interpenetrating polymer because it can be expected to influence hydrogels morphological, swelling, and drug release characteristics (Abdelrazek et al., 2013, Chadha et al., 2006, Domingues et al., 2013, Erizal et al., 2013, Giri et al., 2011, Marsano et al., 2005, Naghdeali and Adimi, 2015, Tomar and Sharma, 2013, Wang and Wang, 2010, Wei et al., 2014, Yanpeng et al., 2006).

Itaconic acid (IA) can be produced from renewable sources by fermentation. IA is very hydrophilic and it expected to show good biocompatibility because of its natural source. Small amounts of IA render good pH sensitivity and increased degree of hydrogel swelling (Bera et al., 2015, Gils et al., 2011, Okabe et al., 2009, Petruccioli et al., 1999, Rashid et al., 2016, Sakthivel et al., 2014, Sariri and Jafarian, 2002, Sudarkodi et al., 2012).

In our work a series of semi-IPN polymeric networks, based on monomers of 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA), with poly(N-vinylpyrrolidone) (PVP) as a interpenetrating agent (P(HEA/IA)/PVP), were synthesized by free radical copolymerization/crosslinking reaction. By introducing highly biocompatible and hydrophilic, chemically inert and electrically neutral PVP, in pH and temperature sensitive HEA/IA copolymer networks, it was expected to obtain excellent biocompatibility with living tissues. The mole fraction of itaconic acid varied in order to determine how the pH sensitivity induced by IA affects the characteristics of the samples. Morphological, thermal, mechanical and swelling properties were examined. The antibacterial activity and cell viability were also tested.

Section snippets

Materials

Monomers 2-hydroxyethyl acrylate (HEA, Aldrich), itaconic acid (IA, Fluka), and polyvinyl pirrolidone (PVP, Aldrich Mw 360000) were used for semi-IPN synthesis. Ethylene glycol dimethacrylate (EGDMA, Aldrich) was used as crosslinking agent, potassium persulfate (PPS, Fluka) as initiator, and N,N, N′,N′-tetramethylene diamine (TEMED, Aldrich) as activator. The polymerization was performed in a water/ethanol mixture. Buffers were prepared using hydrochloric acid (La Chema), potassium chloride

P(HEA/IA)/PVP semi-IPN

Semi-IPNs were obtained by a simultaneous method, where a single crosslinker which has no possibility of any interaction with the second polymer is used. HEA and IA monomers were polymerized simultaneously in the presence of PVP polymer, in such a way that the HEA/IA copolymer is crosslinked and intermingled with PVP linear polymer. TEMED is used as an activator in order to activate polymerization process and EGDMA is used as crosslinker in order to create three-dimensional polymeric network (

Conclusion

Semi-IPN hydrogels based on HEA and IA were synthesized by free radical polymerization with PVP as interpenetrating agent to be used as novel controlled drug release devices. The mole contents of IA varied and the PVP content was constant. The equilibrium swelling behaviors of P(HEA/IA)/PVP samples indicated the remarkable sensitivity to the external pH and temperature. Semi-IPN hydrogel’s properties and parameters (Tg, qe, kinetics—Fickian, non-Fickian, DL, and EE) showed trend with the

Acknowledgment

This work has been supported by the Ministry for Education, Science and Technological Development of the Republic of Serbia (Grants Nos. 172062 and 172026).

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