Novel Polymer Nanometals Carbon Nanofibers Composite Biomaterials

Published Date: 02 Nov 2017

1. INTRODUCTION

The infectious diseases remain a major health problem worldwide causing morbidity and mortality. Decrease in morbidity and mortality because of infectious diseases has been recognized because of the introduction of antibiotics in modern medicine. Remarkable success of early-induced antibiotics has attracted attention towards developing new antibiotics. However, these therapeutic agents are resistant to antibiotics at the critical levels, which may invalidate majority of the clinically used antimicrobial drugs. The changing pattern of infectious diseases and the development of bacterial resistance to many clinically used therapeutic agents have resulted in increased demand of seeking solution to this critical issue [Huh et al 2011, Hogberg et al, 2010, Talyor et al 2002].

Recent focus is to explore the antimicrobial nanomaterials as a bacterial resistant via drug delivery system. In this context, many recent studies focus on some metal nanoparticles (NPs) based drug delivery system. The metal NPs such as Ag, Cu, and Zn etc are known to have antibacterial properties which may be utilized to overcome the infectious diseases [Huh et al 2011, Singh et al 2013]. These NPs have several advantages, for example, insignificant toxicity, small cost and bacterial resistant in comparison with that of the conventional antibacterial agents. Metal NPs are retained much longer in the human body than small molecules of antibacterial agents, which could be effective for sustained therapeutics [Weir et al, 2008, Allaker et al 2008]. The application of nano-biotechnology receiving great interest, different types of nano-materials are currently being used as nanoprobes for drug delivery system and in-vitro diagnostics applications. Recently, advances in the design and modification of nano-materials for drug delivery applications have shown potential for improving the treatment of different infectious diseases. In general, bacterial resistance to antimicrobial agents has been resolved by developing newer material and modifying existing antibiotics agents [Huh et al 2011, Kathryn et al, 1999].

The motivation of developing biocompatible materials having persistent antimicrobial activity emerged following a few recent research activities on the antibiotics drugs loaded with combinations of dental cements and resins. However, the interest in achieving carriers which could deliver active drugs directly at the site of infection was subsequently extended to soluble or pH sensitive polymers [Campoccia et al, 2010, Liu et al, 2009]. Polymers are increasingly being used in several pharmaceutical applications such as binder in drugs and controlled release drug delivery system [Shaik et al, 2012]. Polyvinyl alcohol (PVA) and cellulose acetate phthalate (CAP) are well known biodegradable polymers and contain desirable property such as biocompatibility, and nontoxic. These polymers are widely used in the drug delivery system. PVA are also used in many biomedical applications in contact with tissues and blood such as soft contact lenses, implants of artificial organs, cartilage skin, dialysis membranes, lens, skin, cardiovascular devices, and invertebral discs, because of their excellent flexibility and swelling property in water [Jannesari et al, 2011 and Seabra et al, 2004]. However, biological interaction of the biomaterials including platelet activations, cell adhesion, cell migration and bacteria adhesion consequently determine the biocompatibility of a material [Tsaia et al, 2011].

CAP is widely used as an enteric film coating of drugs, and has antimicrobial as well as antiviral activity such as bacterial vaginiosis, hepatitis and HIV. CAP is not soluble at pH <≈5.8 in water. Because of this unique property it is extensively used in the drugs coating. Blending of polymers is widely used in controlled drug delivery system [Chen et al, 2013, Neurath et al, 2003]. The proposed research work will focuse on the unique properties of the blended polymers with the combination of PVA and CAP as a carrier, with dispersed CNFs as nano-antibiotics.

Carbon nanofiber (CNF) has been extensively studied under recognition as a unique carbon material [Iijima, 1991; Rodriguez et al, 1993 and 1995]. CNFs are carbonaceous nanomaterials used mainly in advanced composite materials to improve strength, stiffness, durability, electrical conductivity, or heat resistance [Darne et al., 2010]. The cost of production of CNF is significantly less than that of carbon nanotubes (CNTs), and therefore, the former offers significant advantages over the latter, providing a high performance to cost ratio.

For the surface-related applications of carbon nanomaterials, it is important to know how surface morphology, structure, and chemistry are effective and how many effective sites the materials possess on the surface. CNF can have a high surface area ranging between 50 to 800 m2/g, if they are catalytically prepared or post-chemically activated [Mekala et al 2012]. CNF composites have been investigated for improving the adhesive properties at the interface between the fiber and the matrix of carbon-fiber reinforced composites and to yield a macroscopic frame or support to be anchored by CNFs to solve handling difficulty and the pressure drop problem [Jahangiri et al 2013, Mekala et al 2012].

The broad utility of nanomaterials results in increased levels of production, however, with increased human exposure and potential release of the materials into the environment. Therefore, much attention is also required for toxicological issues related to nanoparticles, including various fibrous nanomaterials [Shvedova et al., 2010]. CNFs have been widely used as adsorbents and/or metal supports for environmental remediation applications, antimicrobial agents and insignificant toxicity [Ashfaq et al 2013 and Mekala et al 2012]. Advances in nanotechnology and nano-biotechnology have led to an increase in the production of nanomaterials and biomaterials. For blended polymers as a drug carrier, ascertaining the potential toxicity of the prepared polymeric matrices is necessary [Liu et al, 2011]. The properties of nanomaterials are different from those of micron or larger size materials, allowing them to exert novel physical and chemical functional activities [Colvin et al., 2003; Oberdorster et al., 2004]. Nanoparticles can be translocated to the subepithelial space to a greater extent than larger particles [Clurg et al., 1998]. Several studies have reported that small-sized nanoparticles can be translocated from the lungs into the blood [Ashfaq et al, 2013, Donaldson et al., 2001] and can thereby move to other organs and tissues, raising concern that they may cause oxidative stress-mediated toxicity in biological systems [Akhtar et al 2010]. The interactions of particles with cell membranes result in the generation of reactive oxygen species (ROS). The generated oxidative stress may cause a breakdown of membrane lipids, an imbalance of intracellular calcium homeostasis, and DNA breakage [Petruskaet al., 1991; Clutton et al., 1997]. Genotoxic activities may result from direct interaction of particles with the genetic material or secondary damage resulting from particle-induced reactive oxygen species (ROS) production. Both pathways may relate to surface properties, the presence of transition metals, intracellular iron mobilization, or lipid peroxidation processes. Other aspects relevant to primary cytotoxicity are particle size, shape, and the presence of mutagens carried with the particles [Ashfaq et al, 2013, Schins, 2002].

In general, this study aims at the synthesis of new polymeric biomaterial dispersed with the CNFs, and the cytotoxicity and biocompatibility tests of the prepared materials for various applications such as antibiotic discs, wound healing dressing, nano-antibiotics and controlled release drug delivery systems.

2. THE PROPOSED WORK AND OBJECTIVES

The proposed work will focus on Cu and Ag nanoparticles (NPs) dispersed on ACF/CNF, as an antibacterial agents. Polymeric matrices is to be used as a nano-carrier while prepared carbon nanofibers will be used as nano-antibiotics. The preparation of the novel pH sensitive nanocomposite PVA/CAP precursor-based biomaterial dispersed with the web of Cu- and Ag- ACF/CNF is developed for antibacterial application such as antibacterial discs and wound healing dressing. The cytotoxicity of the prepared biomaterials and biocompatibility of the materials will be carried out.

Objectives of the study:

Development of metal nano-particles dispersed carbon micro-nanofibers (CNF) on the substrate activated carbon fibers (ACF).

Synthesis of the polymeric nano-composite biomaterials dispersed with ACF/CNF.

Antibacterial application of the polymeric nano-composite biomaterials.

Evaluation of the toxicity of the prepared polymeric nano-composite biomaterials.

Biological interaction of the serum protein on the prepared polymeric nano-composite biomaterials.

3. WORK PLAN AND METHODOLOGY

In this study preparation of the web of Cu- and Ag- ACF/CNF, monodispersion of metal nitrates on ACF by wet incipient method will be done. The Cu- and Ag- NPs dispersed ACF/CNF will be developed by calcinations, reduction and followed by chemical vapor deposition (CVD) using Cu-and Ag- ACF as the substrate and acetylene (C2H2) as a carbon source [Ashfaq et al, 2013, Singh et al 2013, Mekala et al 2012].

A polymeric matrix will be used as a substrate (carrier). NP-ACF/CNF will be used as antibiotics. CAP will act as pH sensitive, whereas PVA will be used as a good film forming properties. The primary synthesis steps of the antibacterial material will consist of esterification of polyvinyl acetate to produce polyvinyl alcohol gel, ball-milling of the surfactant dispersed Cu- and Ag- ACF/CNF, mixing of the milled micron size fibers to the reactant mixture at the incipience of the polyvinyl alcohol gel formation, and blending of CAP, to produce a film. The prepared polymeric film will be used as antibacterial application as well as diagnostic application. The surface characterization, toxicological evaluation and antibacterial application of prepared materials will be evaluated by using different techniques.

3.1. SURFACE CHARACTERIZTION

After synthesis of material, surface morphology will be examined using scanning electron microscopy, X-ray microanalysis (SEM and EDAX), and atomic force microscopy (AFM). The presence of various functional groups will be confirmed by various instruments such as Fourier Transform Infra-Red Spectrometer (FTIR). Particle size and porosity of polymeric biomaterials and carbon nanofibers will be confirmed by using particle size analyzer and BET/N2 adsorption isotherms. The thermogravimetric analysis will be carried out using thermal gravimetric analysis and differential scanning calorimetry (TGA and DSC) [Mekala B et al 2012, S Singh et al 2013].

3.2. ANTIBACTERIAL ANALYSIS

The antibacterial analysis of the prepared polymeric biomaterials will be analyzed by using different microbiological technique and evaluates MIC and MBC [S Singh et al 2013].

3.3. CYTOTOXICITY ANALYSIS

The in-vitro toxicological evaluations of prepared biomaterials will be carried out by using different techniques such as MTT assay, fluorescence microscopy, oxidative stress associated toxicity parameters and cellular interactions [M Ashfaq et al 2013, Akhtar et al 2010].

4. SIGNIFICANCE OF WORK

The synthesis of the novel polymer-carbon-based nanocomposite as effective antibacterial agents having rapid and sensitive bacterial diagnostics is proposed. The synthesized materials will be used in therapeutics applications. The prepared material will be pH sensitive and water dispersible, which makes the wider applicability of the materials, thus the materials may be used as nano-antibiotics and controlled release drug delivery system. The synthesized polymer-carbon based film contains polymeric matrices used as a carrier whereas the prepared Cu and Ag-ACF/CNF acts as a novel antibiotic. The process of developing these materials is novel, simple and economically viable.