Improvement single-wall carbon nanotubes (SWCNTs) based on functionalizing with monomers 2-hydroxyethylmethacryate (HEMA) and N-vinylpyrrolidone (NVP) for pharmaceutical applications as cancer therapy

Abstract

The functionalized carbon nanotubes play significant roles in the fields such as preparation of composite materials and biological technologies. This paper explains the covalent functionalization of single-wall carbon nanotubes (SWCNTs) with biomedical important monomers, 2-hydroxyethylmethacryate (HEMA) and N-vinylpyrrolidone (NVP) by chemical grafting of HEMA and PVP monomers via free radical polymerization. To get carboxylic acid functionalized SWCNTs, first the nanotubes were oxidized with a mixture of nitric acid and sulfuric acid (1:3). Then, the binding of HEMA and NVP onto the surface of SWCNTs was performed by chemical functionalization of HEMA, NVP with acid chloride-bound carbon nanotube by esterification reaction. These results were confirmed by FT-IR and SEM. The cell culture experiments conducted for pharmaceutical applications were used as cancer therapy.

Introduction

Carbon nanotubes (CNTs) have generated a great interest due to their unique physical and mechanical properties, for example: high young modulus, high thermal conductivity, and large surface area. CNTs are classified into three groups: (1) SWCNTs: it consists of a single graphite sheet that is closed in a tubular shape, (2) DWCNTs, and (3) MWCNTs: they consist of a plurality of graphite sheets, that each sheet is closed into a tubular shape and nested. The SWCNTs and MWCNTs are mostly used. CNTs cannot be widely used in medical and pharmacy because they are insoluble in organic and inorganic solvents [1]. When they enter into the blood, their movement creates some problems. To solve these problems, they are functionalized to increase their solubility, tensile strength, and molecular absorption. To enhance performance of CNTs especially in medical and pharmaceutical fields, they are functionalized with polymers [2]. The functionalization of CNTs depends on the type of polymer and covalent or non-covalent methods. Functionalization is done in two ways: (i) functionalization of sidewall and (ii) functionalization of tail end. In both the methods, CNTs are carboxylate. Terminal carbons are oxidized better than sidewall carbons because of their high curvature. For this purpose, CNTs are mixed with HNO₃ and H₂SO₄.The SWCNTs are used more than the MWCNTs in medical because of their better properties and high turnover in functionalization [3], [4].

Hydrogels are three-dimensional and cross-linked hydrophilic polymers that can absorb and preserve a large amount of water to a great deal of its dry weight. They are very important in a wide variety of applications in medical, pharmaceutical, and related fields, e.g., wound dressings [5], contact lenses [6], artificial organs, and drug delivery systems [7]. Hydrogels are polymeric materials that do not dissolve in water at physiological temperature and pH. They swell considerably in an aqueous medium [8] and prove extraordinary capacity (>20%) for absorbing water within the network structure. Hydrogels in response to change in external conditions such as pH, ionic strength, temperature, and electric currents act as the phase transition are known to “stimuli-responsive” or “smart” gels [9]. Being insoluble, these three-dimensional hydrophilic networks can retain a large amount of water that not only contributes to their good blood compatibility but also maintains a certain degree of structural integrity and elasticity [10]. Hydrogels can be added to functional groups such as OH, COOH, CONH₂, and SO₃H. These compounds can absorb water without being dissolved. Hydrogels can be found in natural or synthetic polymers [11]. Although hydrogels made from natural polymers may not afford adequate mechanical strength and may contain pathogens or evoke immune/inflammatory responses, they display several profitable properties such as natural biocompatibility, biodegradability, and biologically, recognizable moieties that support cellular activities.

Hydrogels have been developed as stimuli-responsive materials, which can endure sudden volume change in response to small changes in environmental parameters: temperature, pH, ionic strength, etc., (Fig. 1). These unique characteristics of hydrogels are of great interest in drug delivery, cell encapsulation, and tissue engineering [12], [13], [14], [15]. The most important systems from a biomedical point of view are those sensitive to temperature and/or pH of the encompassing. The human body exhibits variations of pH along the gastrointestinal tract, and also in some specific areas like certain tissues and subcellular compartments [16].

Both NVP and HEMA are hydrogels polymers which have many applications in medicine and industry. NVP is a water-soluble polymer whose applications for pharmaceutical and cosmetic formulations [17] to technical adhesives, coatings, inks, electronics, etc.,. Currently NVP is used in nanotechnology and nanodrugs especially for the protection and stabilization of metal and metal oxide nanoparticles in aqueous surroundings. For example, mono disperse silver nanotubes were synthesized in large quantities by reducing silver nitrate with ethylene glycol in the presence of NVP [18], [19], [20]. Furthermore, this method allows control over shape and size of gold nanoparticles as well [21]. Two other important roles of NVP are preventing accumulation of nanoparticles and making single-carbon nanotubes easily soluble in water [22], [23], [24]. About cobalt, NVP interacts little with the surface of the particles so that it would not modify their electronic and magnetic properties [25]. Because of its early use as blood plasma extender, for which the range of molar masses must have been adjusted [26], NVP has a long-standing record in biomedical and pharmaceutical applications, and nowadays PVP based drug delivery systems are under intense research [27].

Polymer HEMA is known as important substance that is used extensively in wide range for both industrial and biomedical applications. Because of their super biocompatibility, for instance, molecularly engineered hydrogels based on poly (HEMA) have been shown to be potential carriers in drug delivery, dental, ophthalmic, and neural tissue engineering applications [28], [29], [30]. Also, microspheres prepared from copolymers of poly (HEMA) were reported to have promising applications in the immobilization of several enzymes, and that too, in the isolation of genomic DNA [31], [32]. This suggests that in the future, carbon nanotubes could open up a number of promising pharmaceutical and clinical applications to human [33]. In this paper, we report the synthesis of nanocomposites based on HEMA and NVP polymers and SWCNTs. The polymers were grafted on the surfaces of the SWCNTs using 2,2-azobis(isobutyronitrile) (AIBN) by free-radical polymerization methods [33].