To date, most of the pharmaceutics used have been delivered either orally (as pills or suspensions) or as injectables. However, products that have the ability to control the rate and period of drug delivery and to specifically target various areas of the body for treatment are become increasingly desirable.
There are various drug delivery systems currently being developed and these potentially will give rise to lower drug toxicity, be more site specific and show greater efficacy. These include:
The fate of such delivery systems within the body is determined by a number of properties. Two of the most important are particle size and zeta potential. The particle size of nanoparticles designed for intravenous administration is crucial to the eventual distribution of the drug. Particles in the micrometer size range often get trapped in the lung capillaries and sub 200nm particles with a hydrophilic polymer coating generally accumulate less in the liver and spleen. Knowledge of the zeta potential of a drug delivery system can help to predict the fate of the particle in vivo. Both of these parameters can be measured with light scattering techniques such as Photon Correlation Spectroscopy.
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Presentations:
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On demand presentation on "Predicting Formulation Stability with the Zetasizer Nano System ".
For industries involved in the production of colloidal dispersions, the long-term dispersion stability is an important characteristic of the final product. The stability of a particle dispersion will depend upon the balance of the repulsive and attractive forces that exist between particles as they approach one another. The magnitude of the electrostatic interactions between particles can be determined by measuring the zeta potential of the particle dispersion and hence zeta potential measurements can be used to predict dispersion stability. This presentation describes the application of zeta potential measurements in predicting dispersion stability.
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On demand presentation on "Why measure Zeta Potential?".
This presentation provides an overview of what zeta potential is, what affects it and how it is measured. The use of zeta potential in predicting dispersion stability is also discussed and illustrated with application examples.
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On demand presentation on:"What Affects Dispersion Stability and How Can We Predict It?".
The stability of a particle dispersion is determined by the balance between repulsive and attractive forces which the particles experience as they approach one another. This presentation discusses how dispersion stability can be achieved, what factors influence it and how an understanding of these factors can be used to predict the shelf life of a product.
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Application notes:
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Photon Correlation Spectroscopy and Microemulsions.
Microemulsions are colloidal dispersions that can be used for the solubilisation of drugs. In order to ensure safe and efficient dosage, predictable shelf life and batch to batch consistency, particle size must be closely controlled. One technique that can be used for size determination of microemulsions is that of photon correlation spectroscopy (PCS).
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Size and Zeta Potential Characterization Liposomes on the Zetasizer Nano.
The physical characterization of liposomes is of great importance in understanding their suitability for a range of applications. Knowledge of the zeta potential of a liposome preparation can help to predict the fate of the liposomes in vivo.
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Photon Correlation Spectroscopy and Protein Melting Point Characterization
The sensitivity of Photon Correlation Spectroscopy is sufficient to distinguish different oligomeric and quaternary protein states, and is ideally suited for monitoring the stability of the protein structure to denaturing conditions.
Proteins are composed of polypeptide chains with unique 3-dimensional structures in the native state. These structures are stabilized by a combination of electrostatic and hydrophobic interactions, combined with a large degree of flexibility inside the structure of the molecule. If solution conditions change, denaturation or unfolding can quickly occur, along with a subsequent change in size. The sensitivity of dynamic light scattering is ideally suited for monitoring the stability of a protein to denaturing conditions. The protein melting point temperature is indicative of the thermal stability of a protein. Modifications (such as glycosylation) can influence the stability and are easily observed with dynamic light scattering. |
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Characterization of Protein Polyelectrolyte Complexes.
This application note highlights the use of the Malvern Zetasizer Nano system for characterization of proteinpolyelectrolyte complexes (PPCs).
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Photon Correlation Spectroscopy and Drug Screening for Promiscuous Inhibitors
New lead compounds for drug design are typically discovered using high throughput combinatorial techniques that utilize large screening databases of known compounds. These small molecule databases however, have been shown to contain promiscuous inhibitors that function as effective enzyme inhibitors, while exhibiting non drug-like traits such as poor specificity and uncorrelated structure-function relationships. Recent studies indicate that the concentration dependent inhibitory nature of these promiscuous inhibitors is a direct consequence of non-specific aggregation, i.e. when the molecule is aggregated it functions as an effective inhibitor; when aggregation is absent, so is the inhibitory activity of the compound. While the mechanism for this aggregation controlled inhibition is still under examination, the suggested pathway is one wherein the enzyme absorbs either onto the surface or into the interior of the drug aggregate, which subsequently restricts active site access. Photon correlation spectroscopy or dynamic light scattering (DLS) is an analytical technique capable of measuring the size of very small particles, at low sample concentrations. Because of the molecular weight dependence of the particle scattering intensity, the technique is extremely sensitive to the presence of aggregates. As such, Photon Correlation Spectroscopy isan ideally suited screening tool for identifying promiscuous inhibitors from the cache of lead compound candidates selected from small molecular databases. This application note summarizes measurements performed on a candidate drug that exhibits inhibitory behavior at certain concentrations..
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Use of Zeta Potential Measurements to Study Sterically Stabilised Liposomes.
Liposomes are vesicles in which an aqueous volume is entirely enclosed by a membrane composed of lipid molecules, usually phospholipid. They can be prepared so that they entrap materials both within their aqueous compartment (water-soluble materials) and within the membrane (oil-soluble materials). They are extensively used as vehicles for the targeted delivery of drugs. The fate of intravenously injected liposomes is determined by a number of properties. Two of the most important are particle size and zeta potential.
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Photon Correlation Spectroscopy and Zeta Potential Characterization of Model Drug Carriers.
This research work uses a Malvern Zetasizer to characterize the size and surface properties of polystyrene latex when coated with various polymers. The measurements are done in both dilute salt and serum.
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Characterization of Colloidal Drug Carrier Systems with Zeta Potential Measurements.
Article published in "Pharmacuetical Technology Europe" January 1999.
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Emulsions: Predicting the Stability of Emulsions.
Measurements of zeta potential, along with particle size, can be used to predict the stability of fat emulsions.
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