Definition, History, And Evaluation Of Nanoparticles

Definition

“Nanoparticles are sub-nanosized colloidal structures composed of synthetic or semi-synthetic. Particle of any shape with dimensions in the 1 × 10−9 and 1 × 10−7 m range Nanoparticles are particles between 1 and 100 nanometres (nm) in size with a surrounding interfacial layer. The term "nanoparticle" is not usually applied to individual molecules; it usually refers to inorganic materials. Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures.

A bulk material should have constant physical properties regardless of its size, but at the nano-scale this is often not the case. Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials. The properties of materials change as their size approaches the nanoscale and as the percentage of atoms at the surface of a material becomes significant. For bulk materials larger than one micrometre the percentage of atoms at the surface is minuscule relative to the total number of atoms of the material. The interesting and sometimes unexpected properties of nanoparticles are not partly due to the aspects of the surface of the material dominating the properties in lieu of the bulk properties. Nanoparticles exhibit a number of special properties relative to bulk material. For example, the bending of bulk copper (wire, ribbon, etc. ) occurs with movement of copper atoms/clusters at about the 50-nm scale.

According to ISO Technical Specification 80004, a nanoparticle is defined as a nano-object with all three external dimensions in the nanoscale, whose longest and shortest axes do not differ significantly, with a significant difference typically being a factor of at least 3.

Introduction

Although nanoparticles are associated with modern science, they have a long history. Nanoparticles were used by artisans as far back as Rome in the fourth century in the famous Lycurgus cup made of dichroic glass as well as the ninth century in Mesopotamia for creating a glittering effect on the surface of pots. In modern times, pottery from the Middle Ages and Renaissance often retains a distinct gold- or copper-coloured metallic glitter. This lustre is caused by a metallic film that was applied to the transparent surface of a glazing. The lustre can still be visible if the film has resisted atmospheric oxidation and other weathering.

The lustre originates within the film itself, which contains silver and copper nanoparticles dispersed homogeneously in the glassy matrix of the ceramic glaze. These nanoparticles are created by the artisans by adding copper and silver salts and oxides together with vinegar, ochre, and clay on the surface of previously-glazed pottery. The object is then placed into a kiln and heated to about 600 °C in a reducing atmosphere. In heat the glaze softens, causing the copper and silver ions to migrate into the outer layers of the glaze. There the reducing atmosphere reduced the ions back to metals, which then came together forming the nanoparticles that give the colour and optical effects.

Lustre technique showed that ancient craftsmen had a sophisticated empirical knowledge of materials. The technique originated in the Muslim world. As Muslims were not allowed to use gold in artistic representations, they sought a way to create a similar effect without using real gold. The solution they found was using lustre.

Michael Faraday provided the first description, in scientific terms, of the optical properties of nanometre-scale metals in his classic 1857 paper. In a subsequent paper, the author (Turner) points out that: "It is well known that when thin leaves of gold or silver are mounted upon glass and heated to a temperature that is well below a red heat (~500 °C), a remarkable change of properties takes place, whereby the continuity of the metallic film is destroyed. The result is that white light is now freely transmitted, reflection is correspondingly diminished, while the electrical resistivity is enormously increased. "

Advantages

1. Nanoparticles drug carriers have higher studies.
2. Nanoparticles have higher carrier capacity.
3. Feasibility of variable routes of administration.
4. Improves stability and therapeutic index and reduce toxic effect.
5. Nano particles can be administered by parenteral, oral, nasal, ocular routes.
6. Nanoparticles can be used for controlled delivery of drugs.

Disadvantages

• Toxic metabolites may form on repeated administration.
• The polymeric nanoparticles are relatively slowly biodegradable which might cause systemic toxicity.
• Small size and large surface area can lead to particle aggregation.
• Antigenicity and batch to batch variation.

Evaluation of nanoparticles

Particle size

Particle size plays major role in determining the in vivo distribution, biological fate, toxicity and the targeting ability of nano systems. In addition, they can also influence the drug loading, drug release and stability of nanoparticles. It is important to study the size and surface characteristics of the drug particle or drug loaded carrier to determine the drug delivery at the target site.

Photon correlation spectroscopy (PCS): For smaller particle. Photon Correlation Spectroscopy (PCS) is a novel technique that exploits a coherent X-ray synchrotron beam to measure the dynamics of a sample. By recording how coherent speckle fluctuations in time, one can measure a time correlation function, and thus measure the timescale processes of interest (diffusion, relaxation, reorganization, etc. ). PCS is used to study the slow dynamics of various equilibrium and non-equilibrium processes occurring in condensed matter systems. It is also known as Dynamic Light Scattering or Quasi Elastic Light Scattering (QELS) records the variation in the intensity of scattered light on microsecond time scale. This variation results from interference of light scattered by individual particles under the influence of Brownian movement and is quantified by compilation of an autocorrelation function. This function is fit to an exponential, or some combination with the corresponding decay constant being relation to the diffusion coefficient using standard assumptions of spherical size, low concentrations and known viscosity of the suspending medium, particle size is calculated from this coefficient.

Laser diffractometry: Laser diffraction analysis, also known as laser diffraction spectroscopy, is a technology that utilizes diffraction patterns of a laser beam passed through any object ranging from nano meters to milli meters in size to quickly measure geometrical dimensions of a particle. This process does not depend on volumetric flow rate, the amount of particles that passes through a surface over time.

Electron microscopy: The electron microscope is a type of microscope that uses a beam of electrons to create an image of the specimen. It is capable of much higher magnifications and has a greater resolving power than a light microscope, allowing it to see much smaller objects in finer detail. They are large, expensive pieces of equipment, generally standing alone in a small, specially designed room and requiring trained personnel to operate them. Required coating of conductive material such as gold and limited to dry sample.

Transmission electron microscope: Easier method and permits differenciation among nano capsules and nanoparticles. Transmission electron microscopes are capable of imaging at a significantly higher resolution than light microscopes, owing to the smaller de Broglie wavelength of electrons. TEM works on the same principle as SEM, but in TEM a focussed monochromatic beam of electrons is transmitted through the sample. During transmission, it interacts with the sample similar to SEM. This transmitted electron beam is focused into a image and projected on to a phosphor emitting screen. The magnification of TEM is up to 50000X. through similar in principle SEM and TEM have few differences.

Atomic force microscope: Atomic force microscopy (AFM) or scanning force microscopy(SFM) is a very-high-resolution type of scanning probe microscopy(SPM), with demonstrated resolution on the order of fractions of a nanometre, more than 1000 times better than the optical diffraction limit.

Scanning electron microscope: A scanning electron microscope (SEM) is a type of electron microscope that produces images of a sample by scanning the surface with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that contain information about the sample's surface topography and composition. The electron beam is scanned in a raster scan pattern, and the beam's position is combined with the detected signal to produce an image. SEM can achieve resolution better than 1 nanometre. Scanning electron microscope is very useful to visualize nanoparticles. The microscope works under vacuum. Hence, samples need to be prepared carefully and special procedures need to be adopted. Biological samples need drying to prevent shrivelling. The sample should also be conductive to electricity as it is illuminated by an electron beam. Usually sputter coated is used to coat the sample with a thin layer of gold to impart these properties. To start scanning vacuum is created in the column, followed by a beam of high energy electrons generated by an electron gun. This beam travels downwards.

Density

Density gradient centrifugation: Density gradient centrifugation can be performed either as rate zonal or as isopyknic centrifugation. In rate zonal centrifugation, the particles sediment as a narrow zone through a preformed gradient. This technique is used analytically for sedimentation rate measurements, and preparatively for separation of particles with different sedimentation coefficients. In isopyknic centrifugation, particles are separated purely on the basis of their density. Isopyknic centrifugation can be carried out both in preformed and in self-forming gradients. In self-forming gradients, the sample is mixed with the gradient medium, centrifuged, and as the solute molecules sediment to form the gradient, the sample molecules band at their isopyknic points. When preformed gradients are used, the size of the particles will affect the rate at which they reach their isopyknic positions.

Molecular weight

Gel permeation chromatography using refractive index detector.

Structure & crystallinity

X-Ray Diffraction: X-ray diffraction (XRD) is one of the most important non-destructive tools to analyse all kinds of matter — ranging from fluids, to powders and crystals. From research to production and engineering, XRD is an indispensable method for materials characterization and quality control. It is also used for determining change in physical state and extent of amorphous drug.

Thermoanalytical method: such asDifferential scanning calorimetry: determines the crystalline structure when nano suspensions are prepared drug particles get converted to amorphous form hence it is essential to measure the extent of amorphous drugs generated during the production of nano suspensions.

Differential thermal analysis: Differential thermal analysis(or DTA) is a thermoanalytic technique that is similar to differential scanning calorimetry. In DTA, the material under study and an inert reference are made to undergo identical thermal cycles, (i. e. , same cooling or heating programme) while recording any temperature difference between sample and reference.

Thermogravimetry: Thermogravimetric analysis or thermal gravimetric analysis(TGA) is a method of thermal analysis in which the mass of a sample is measured over time as the temperature changes. This measurement provides information about physical phenomena, such as phase transitions, absorption and desorption; as well as chemical phenomena including chemisorption’s, thermal decomposition, and solid-gas reactions.

Specific surface area

Sorptometer: Volumetric and continuous-flow methods are utilized to characterize samples for the physical properties named under the Tests section. For all precision volumetric instruments, the equilibrium volume of a gas adsorbed on a sample can be determined by measuring the decrease in pressure of a known volume of adsorbate gas at a controlled pressure and temperature. This decrease in pressure is the result of the expansion of the adsorbate gas as it is released from the manifold to the sample cell and from gas actually adsorbing on to the sample specific surface area A = 6 / density X diameter of particle.

Surface charge

Electronic mobility: surface charge of particle can be determined by measuring particle velocity in electric field laser doppler anemometry tech. for determination of nanoparticles velocities surface charge is also measured as electrical mobility.

Charged composition critically decides bio-distribution of Nano particles. Zeta potential can also be obtained by measuring the electronic mobility.

Surface hydrophobicity

Important influence on interaction of nano particles with biological environment. Several methods have been used Hydrophobic interaction chromatography.

Invitro release

Diffusion cell: Diffusion of the drug from the semisolid product across the membrane is monitored by assay of sequentially collected samples of the receptor medium. Recently introduce modified ultra-filtration tech: Media used: phosphate fibre.

Conclusion

Nano particles are one of the novel drug delivery systems, which can be potential use in controlling and targeting drug delivery as well as in cosmetics, textiles and paints. Judging by the current interest and previous successes, nanoparticulate drug delivery systems seems to be a viable and promising strategy for the biopharmaceutical industry.