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Differential Scanning Calorimetry (DSC) Platform for Nucleic Acid Drugs

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Differential Scanning Calorimetry (DSC) is a technique used to directly characterize the stability of nucleic acid molecules in their natural state. CD Formulation offers a DSC technology platform that enables customers to obtain accurate, high-quality data, providing critical insights into the stability of nucleic acids during process development.

About Differential Scanning Calorimetry (DSC) Technology

Differential Scanning Calorimetry (DSC) is a powerful thermal analysis technique used for quantitative calorimetric measurements of solid, liquid, or semi-solid samples. A typical DSC scan involves heating a sample at a controlled, steady rate while monitoring the heat flow to characterize phase changes and solidification reactions as the temperature increases.

DSC is a powerful technique used to determine a wide range of thermodynamic and kinetic parameters, including specific heat capacity, heat of reaction, heat of transition, phase diagrams, reaction rates, crystallization rates, polymer crystallinity, sample purity, and more.

Key Considerations for DSC Technology

Considerations Descriptions
Sample Requirements Solid and liquid samples can be analyzed.
Solid samples may be in the form of powder, flakes, crystals, or granules.
Influence of Sample Dosage A small dosage is effective for rapid programmed temperature scanning, as it provides high resolution and enhances the qualitative effects. It also facilitates the release of cleavage products and achieves high transition energy. Conversely, a larger dosage allows for the observation of minor transitions and yields more accurate quantitative results.
Influence of Shape The geometry of the sample also affects the shape of the DSC peaks. Larger samples tend to exhibit irregular peak shapes due to inadequate heat transfer, while thinner or finer samples display regular peak shapes, which are advantageous for area calculations.
Purity of Sample The purity of the sample significantly affects the DSC curve. An increase in impurity content will cause the transition peak to shift toward lower temperatures, resulting in a broader peak shape.

Types of DSC Platform for Nucleic Acid Drugs

Fig.1 Types of DSC platform for nucleic acid drugsFig.1 Types of DSC Platforms. (CD Formulation)

Conventional Differential Scanning Calorimetry (DSC) Platforms

Conventional DSC platforms are extensively utilized to evaluate the thermal stability of nucleic acid drugs. By measuring the heat absorption and exothermic reactions of a sample during heating, conventional DSC can determine the melting temperature (Tm) of a nucleic acid drug.

Micro-Differential Scanning Calorimetry (Micro-DSC) Platforms

Micro-DSC is a highly sensitive DSC platform designed for analyzing trace nucleic acid samples. It offers more precise thermodynamic parameters and is well-suited for investigating the thermodynamic changes associated with nucleic acid molecular interactions, such as ligand binding and metal ion binding.

High-Throughput Differential Scanning Calorimetry (DSC) Platforms

The high-throughput DSC platform enables the simultaneous analysis of multiple nucleic acid samples, significantly enhancing experimental efficiency. This platform is ideal for large-scale screening of nucleic acid drug candidates, allowing for the assessment of their thermal stability and interaction properties.

Modulated Differential Scanning Calorimetry (MDSC) Platforms

MDSC is an advanced temperature modulation technique derived from conventional DSC. It effectively separates reversible and irreversible components of complex thermal effects. In the analysis of nucleic acid drugs, MDSC offers enhanced insights into baseline drift, changes in heat capacity, and melting behavior.

Pressure-Controlled Differential Scanning Calorimetry (DSC) Platforms

The pressure-controlled DSC platform can conduct thermal analysis under varying pressure conditions, making it ideal for investigating the impact of high-pressure environments on the thermal stability of nucleic acid drugs. By simulating in vivo high-pressure conditions, the pressure-controlled DSC aids in predicting the performance of nucleic acid drugs under specific physiological circumstances.

Highlights of DSC Platform for Nucleic Acid Drugs

  • DSC analysis can detect minute changes in thermal effects in samples with high sensitivity, yielding accurate data.
  • Differential Scanning Calorimetry (DSC) is a non-destructive analytical technique in which the sample remains intact and is not consumed during the analysis.
  • The method is applicable not only to solid samples but also to samples in liquid and solution states for thermal analysis.
  • Detailed thermodynamic parameters, such as enthalpy change, entropy change, and heat capacity, can be obtained through differential scanning calorimetry.

Our Analytical Characterization Services

CD Formulation's DSC platform for nucleic acid pharmaceuticals emphasizes a thorough evaluation of their thermophysical properties. By precisely measuring the heat flow into or out of a nucleic acid sample as a function of temperature or time, DSC can yield critical information regarding the glass transition temperature, melting temperature, and thermal stability of nucleic acid drugs.

Identification of Nucleic Acid Drugs

By analyzing the relationship between temperature and changes in heat flow, DSC can accurately identify the characteristic peaks of nucleic acid drugs, thereby enabling the determination of their composition and structure.

Stability Analysis for Nucleic Acid Drugs

DSC is also utilized for the stability analysis of nucleic acid drugs. By assessing the thermodynamic behavior of a sample at various temperatures, it is possible to determine its thermal stability, as well as its stability during storage.

Melting Temperature (Tm) Testing for Nucleic Acid Drugs

By measuring the change in heat flow during the melting process of a sample, DSC can accurately determine the melting point of a nucleic acid drug. This technique not only aids in understanding the physical properties of the drug but also provides essential data for optimizing the manufacturing process.

Moisture Content Determination for Nucleic Acid Drugs

By analyzing the variations in heat flow of a sample at different temperatures, the processes of removing water of crystallization and adsorbed water can be differentiated, allowing for accurate determination of their respective contents. This has significant applications in quality control of formulations for nucleic acid drugs.

Publication Data

Technology: DSC platform for analyzing nucleic acids

Journal: Nucleic acids research

IF: 16.6

Published: 2008

Results:

The authors characterized 36 quadruplex sequences from the promoter regions of various proto-oncogenes using CD, UV light and native gel electrophoresis. The authors investigated the folding topology and determined the thermodynamic characteristics of quadruplex sequences with different total loop lengths (5-18 bases) and compositions. The results show that both the loop length and its composition affect the quadruplex structure and thermodynamics, making it difficult to establish a universal link between loop length and thermodynamic stability. In addition, the authors compared the thermodynamic stability of the quadruplex and its respective double strand to understand the competition between the quadruplex and the double strand.

Fig.2 DSC platform for analyzing nucleic acidsFig.2 Representative DSC curves for different quadruplexes.

CD Formulation's DSC analysis is an essential tool for materials characterization. It uncovers vital material properties, empowering researchers and industry professionals to make informed decisions, optimize processes, and ensure the highest quality products across various material classes. Contact us to learn how DSC analysis can enhance your understanding of nucleic acid drugs.

References

  1. Kumar N, Maiti S. A thermodynamic overview of naturally occurring intramolecular DNA quadruplexes. Nucleic Acids Res. 2008, 36(17): 5610-5622.
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