Nasir M. Ahmad

Silica-based nanoparticles for biomedical applications.

In this short review we highlight novel uses of silica-based nanoparticles (NPs) in the biomedical sector. Silica NPs are widely used in nanotechnology because they are easy to prepare and inexpensive to produce. Their specific surface characteristics, porosity and capacity for functionalization make them good tools for biomolecule detection and separation, providing solid media for drug delivery systems and acting as contrast agent protectors. In addition, they are used as safety and biocompatible pharmaceutical additives. Here, we focus on novel techniques based on silica NPs for the most important biomedical applications.

Magnetic nanoparticles: In vivo cancer diagnosis and therapy.

Recently, significant research efforts have been devoted to the finding of efficient approaches in order to reduce the side effects of traditional cancer therapy and diagnosis. In this context, magnetic nanoparticles have attracted much attention because of their unique physical properties, magnetic susceptibility, biocompatibility, stability and many more relevant characteristics. Particularly, magnetic nanoparticles for in vivo biomedical applications need to fulfill special criteria with respect to size, size distribution, surface charge, biodegradability or bio-eliminability and optionally bear well selected ligands for specific targeting. In this context, many routes have been developed to synthesize these materials, and tune their functionalities through intriguing techniques including functionalization, coating and encapsulation strategies. In this review article, the use of magnetic nanoparticles for cancer therapy and diagnosis is evaluated addressing potential applications in MRI, drug delivery, hyperthermia, theranostics and several other domains. In view of potential biomedical applications of magnetic nanoparticles, the review focuses on the most recent progress made with respect to synthetic routes to produce magnetic nanoparticles and their salient accomplishments for in vivo cancer diagnosis and therapy.

Novel Azobenzene-Functionalized Polyelectrolytes of Different Substituted Head Groups 3: Control of Properties of Self-Assembled Multilayer Thin Films

Novel azobenzene polyelectrolytes have been used to fabricate biocompatible self-assembled multilayer (SAMU) thin films of variable absorbance, thickness, organization, and morphology. The prepared SAMU films are useful for directed cell growth, and this application relies directly on control of contact and surface energy, and requires the ability to tune the surface characteristics which are critical to their development. The azo polyelectrolytes employed here were similar in their degree of polymerization and repeat unit composition of acrylic acid monomer and azo monomers, and only differ from each other due to the presence of different substituted head R-groups present on the p-position of the aromatic ring of the azo chromophores. Possession of characteristics of both the self-assembly due to acrylic acid groups, and photoswitchability of the azo monomer enable the azobenzene functionalized polyelectrolytes to exhibit novel photo-reversible applications. The azo polyelectrolytes with the substituted R-group pairs of shorter-ionized hydrophilic COOH and SO3H, shorter-non-ionized hydrophobic H and OC2H5, and larger-nonionized hydrophobic octyl C8H17 and C8F17 were used as polyanions and counter charge PDAC used as polycation to fabricate the layer-by-layer SAMU films onto glass and silicon substrates. The fabricated SAMU films were also characterized by various techniques. The UV absorption maxima, λmax p of the SAMU films move to lower wavelength relative to solution to exhibit a blue shift for the hydrophobic R-groups, while this behaviour was not observed for the hydrophilic R-groups. Similarly, the thickness, organization, morphology and other properties of the thin films were found to be dependent on the type of substituted R-groups of the azo polyelectrolytes due to the inter-related factors of ionization, hydrophobicity/hydrophilicity, solubility, and aggregation of azo PEL in the dipping solutions used for fabrication of the SAMU films. Understanding and controlling the adsorption characteristics of azo multilayer thin–film of switchable functionalities are vital to explore their potential for the development and application of new devices in diverse areas of biosensor, drug delivery systems, on-chip microscale chemical process and microfluidics systems.

Novel Azobenzene-Functionalized Polyelectrolytes of Different Substituted Head Groups 2: Control of Surface Wetting in Self-Assembled Multilayer Films

A novel set of light-responsive polyelectrolytes has been developed and studied, to control and tune surface wettability by introducing various types of substituted R head-groups of azo polyelectrolytes in self-assembled multilayer (SAMU) films. As part of a larger project to develop polymer surfaces where one can exert precise control over properties important to proteins and cells in contact, photo-reversibly, we describe here how one can tune quite reliably the contact angle of a biocompatible SAMU, containing a photo-reversible azo chromophore for eventual directed cell growth. The azo polyelectrolytes described here have different substituted R head-group pairs of shorter-ionized hydrophilic COOH and SO3H, shorter non-ionized hydrophobic H and OC2H5, and larger non-ionized hydrophobic octyl C8H17 and C8F17, and were employed as polyanions to fabricate the SAMU onto silicon substrates by using the counter-charge polycation PDAC. The prepared SAMU films were primarily characterized by measurement of their contact angles with water. The surface wetting properties of the thin films were found to be dependent on the type of substituted R-groups of the azo polyelectrolytes through their degree of ionization, size, hydrophobicity/hydrophilicity, solubility, conformation, and inter-polymeric association and intra-polymeric aggregation. All these factors appeared to be inter-related, and influenced variations in hydrophobic/hydrophilic character to different extents of aggregates/non-aggregates in solution because of solvation effects of the azo polyanions, and were thus manifested when adsorbed as thin films via the SAMU deposition process. For example, one interesting observation is significantly higher contact angles of ⩾79° for SAMU films of larger octyl R groups of PAPEA-C8F17 and PAPEA-C8H17 than for others with contact angles of ⩽64° observed for non-polar R-groups of OC2H5 and H. Furthermore, lower contact angle values of ⩽59° for SAMU films with polar R-groups of COOH and SO3H relative to that of non-polar R-groups are in accordance with their expected order of the hydrophilicity or hydrophobicity. It is possible that the large octyl groups are more effective in shielding the ionic functional groups on the substrate surface, and contributed less to the water drop-molecule interactions with ionic groups of the PDAC and/or AA groups. In addition, higher hydrophobicity of the SAMU films may be due to the incorporation of bulky and hydrophobic groups in these polyelectrolytes, which can produce aggregates on the surfaces of the SAMU films. Through understanding and controlling the complex aggregation behavior of the different substituted R-groups of these azo polyelectrolytes, and hence their adsorption on substrates, it appears possible to finely tune the surface energy of these biocompatible films over a wide range, enhance the photo-switching capabilities of the SAMU films, and tailor other surface properties for the development and application of new devices in diverse areas of microfluidics, specialty coatings, sensors, and biomedical sciences.

Novel Azobenzene-Functionalized Polyelectrolytes of Different Substituted Head Groups 1: Synthesis, Characterization and Absorption Spectroscopy Studies

A new class of a series of amphiphilic polyelectrolytes functionalized with azobenzene chromophores have been synthesized and thoroughly characterized by various techniques. A facile two stage strategy is developed, and first involved the preparation of a precursor base polymer, designated as P(APEA), by the free-radical copolymerization of the monomers of acrylic acid (AA) and 2-(phenylethylamino)ethyl acrylate (PEA). In the second step, precursor PAPEA polymers are reacted and post-polymer modified with the diazonium salts to synthesize azobenzene polyelectrolyte, PAPEA-R with different substituted R-groups present on the para position of the aromatic ring of the azo chromophores. The PAPEA-R polyelectrolytes are same in their degree of polymerization and repeat unit compositions of AA and PEA monomers, and only differ from each other by the type of R-groups. The copolymers were classified on the basis of the characteristics of their R-groups into the hydrophilic-ionizeable smaller pair of ─SO3H and ─COOH, the hydrophobic-non-ionizeable smaller pair of ─ H and ─OC2H5, and the hydrophobic-non-ionizeable larger octyl pair of ─C8H17 and ─ C8F17. The prepared copolymers are also characterized by NMR spectroscopy for structure, GPC for molecular weight, and UV-Visible spectroscopy for absorption determination. In DMF solvent, approximately similar absorption maxima, (λmax) values were observed for azo chromophore-containing monomers and after incorporating these into their corresponding polymers structures. However, for the self-assembled multilayer thin films, λmax moved to lower wavelengths to exhibit a blue shift with hydrophobic R-group of ─C8H17, while this behaviour was not observed for hydrophilic R-group of ─COOH. The shift in λmax is found to be highly dependent on the type of substituted R-group, and attributed to aggregation of hydrophobic azo chromophores in DMF:H2O mixture employed for self-assembly. The presence of the ionizeable AA and light-sensitive azo-chromophore functionalized PEA monomers in the PAPEA-R polyelectrolytes impart self-assembling and photoswitchable characteristics, respectively. Through understanding and controlling the solubility and complex solution aggregation behaviour of the different substituted R-groups of azo PEL, their adsorption, thickness, morphology, wetting, molecular-control, and photoresponsiveness can be tailored to enhance the capabilities of the self-assembled multilayer film process in diversified areas of microfluidics, sensing, and controlled release.

Synergistic effect of Chitosan-Zinc Oxide Hybrid Nanoparticles on antibiofouling and water disinfection of mixed matrix polyethersulfone nanocomposite membranes

Antifouling polyethersulfone (PES) membranes for water disinfection were fabricated by incorporating varying concentrations of carbohydrate polymer chitosan and Zinc oxide hybrid nanoparticles (CS-ZnO HNPS). The CS-ZnO HNPS were prepared using chemical precipitation method and were characterized using SEM, XRD and FTIR. The membranes were then fabricated by incorporating nanoparticles of CS-ZnO HNPS with three different concentrations of 5%, 10% and 15% w/w in the casting solution of PES through phase inversion method. The influence of nano-sized CS-ZnO HNPS on the properties of PES was characterized to study morphology, contact angle, water retention, surface roughness and permeability flux. The membranes with the maximum concentrations of 15% HNPS resulted in larger mean pore sizes and lowest contact angle value as compare to the pristine PES membrane. The prepared membranes exhibited significant water permeability, hydrophilicity and prevention against microbial fouling. The prepared membranes were observed to have significant antibacterial as well as antifungal properties due to the synergistic effect of chitosan and ZnO against both bacteria of the type of S. Aureus, B. Cereus, E. coli, and fungi such as S. typhi, A. fumigatus and F. solani.

In vitro MRI of biodegradable hybrid (iron oxide/polycaprolactone) magnetic nanoparticles prepared via modified double emulsion evaporation mechanism

Hybrid magnetic particles are being applied in biomedical field for various aims. One of such aim is use of magnetic particles for diagnostic purposes especially in imaging mechanisms. In vitro magnetic resonance imaging of biodegradable hybrid (iron oxide/polycaprolactone) magnetic nanoparticles is carried out. Hybrid magnetic nanoparticles were prepared by encapsulation of iron oxide nanoparticles (IONPs) in polycaprolactone (PCL) via modified double emulsion evaporation technique. Both the IONPs and hybrid nanoparticles were characterized for their sizes, zeta potential, microscopic, thermogravimetric, and magnetism. Prepared particles were investigated for T1 and T2 weighted enhancement of contrast in vitro in water. A comparison of the prepared particles was done with commercially available Gadolinium for the contrast efficiency in MRI. Results showed the prepared particles exhibited nanosize range, good morphology and superparamagnetic character. The enhancement in the MRI contrast of the prepared particles was observed and found to depend on type of the prepared particles. Comparison of the MRI contrast of the prepared particles with the commercial Gadolinium suggests their usefulness as T2 contrast agent.

Synthesis, Structural, Electrical, Magnetic and Dielectric Spectroscopic Characterization of C-Er2Si2O7

The Polymorphic Er2Si2O7 Is Synthesized by Solid State Double Sintering Method. Structural and Morphological Characterizations Have Been Performed Using X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The Electrical Characterization Has Been Performed by Two Probe Method as a Function of Temperature. the Dielectric Spectroscopic Measurements of Polymorphic Er2Si2O7 Are Performed in the Temperature Range 300-555 K and Frequency Range 3 kHz to 1 MHz. the dc Electrical Transport Data Are Analyzed According to Mott’s Variable-Range Hopping. The ac Conductivity σac(ω) Is Obtained through the Dielectric Spectroscopic Measurements. the ac Conductivity Obeys Power Law which Can Be Expressed as σac (ω) = B ωs, where S Is Slope and it Determines the ac Electrical Transport Phenomenon. the ac Electrical Transport Data and its Variation with Temperature in this Rare Earth Formulation Are Well Discussed. the Magnetic Behavior of Synthesized Material Is Analyzed and Confirmed that Material Have Non-Magnetic Behavior with Coercivity (Hc) 842 Oe. while the Values of Magnetic Saturation (MS) and Remanace (Mr) Were Found in Range 3.90emu/g and 1.07emu/g.

Aminodextran polymer-functionalized reactive magnetic emulsions for potential theranostic applications

Aminodextran (AMD) polymer was prepared via chemical grafting of hexamethylenediamine on oxidized dextran. Magnetic latex particles were successfully obtained by adsorption of positively charged AMD on negatively charged submicron magnetic emulsion. The adsorbed amount was found to be ranged from 20 to 1280mg of AMD per gram of dried magnetic dispersion. The AMD-coated magnetic emulsions were characterized by positive zeta potential in the pH range from 3 to 9 compared to bare seed magnetic emulsion. All the samples showed to be superparamagnetic property, even after the adsorption of the polymer. The developed magnetic submicron particles exhibited good potential for in vivo biomedical diagnosis applications as demonstrated by their higher T2 contrast-ability compared to Gd in magnetic resonance imaging (MRI) and hyperthermia.

CHAPTER 9:Soft Hybrid Nanoparticles: from Preparation to Biomedical Applications

Hybrid particles are a class of materials that include both organic and inorganic moieties at the same time and possess interesting magnetic, optical and mechanical properties. Extensive research is being carried out to develop soft hybrid nanoparticles utilizing their superparamagnetic, biodegradable and fluorescence properties and to explore their biomedical applications. This chapter discusses the important methods for the development of different types of soft hybrid nanoparticles, including polymer immobilization on preformed particles, adsorption of polymers on colloidal particles, adsorption of polymers via layer-by-layer self-assembly, adsorption of nanoparticles on colloidal particles, chemical grafting of preformed polymers, polymerization from and on to colloidal particles, click chemistry, atom-transfer radical polymerization (ATRP), reversible addition–fragmentation chain-transfer radical (RAFT) polymerization, nitroxide-mediated polymerization (NMP) and conventional seed radical polymerization. With current rapid advances in nanomedicine, colloidally engineered hybrid particles are gaining immense importance in fields such as cancer therapy, gene therapy, disease diagnosis and bioimaging. The applications of soft hybrid nanoparticles with respect to diagnosis are discussed briefly and a comprehensive account of their applications in the capture and extraction of nucleic acids, proteins and viruses is presented in this chapter.