Deagglomeration of DNA nanomedicine carriers using controlled ultrasonication

Analytik reports on research from the National Physical Laboratory (NPL) who have developed a method to achieve controlled de-agglomeration of drug delivery nanoparticle systems which is reproducible and scalable.

The Surface Technology, Ultrasound and Underwater Acoustic and Biometrology Groups at NPL, in collaboration with company N4 Pharma, have published: “Deagglomeration of DNA nanomedicine carriers using controlled ultrasonication” in the peer reviewed journal Ultrasonic Sonochemistry.

In the method, highly engineered silica particles are deagglomerated with and without the presence of plasmid, achieved via sonication using controlled cavitation in a multi-transducer vessel.

Characterisation of the resulting size distributions of the particles was achieved using a combination of laser diffraction (LD) and differential centrifugal sedimentation (DCS). DSC was performed using the CPS Disc Centrifuge  from Analytik, to ‘show the utility of laser diffraction and differential centrifugal sedimentation in quantifying the efficacy of product de-agglomeration in the microscale and nanoscale size range respectively.’

DCS measures the time it takes particles to sediment through a fluid of known density in a centrifugal field. During sedimentation, the particles separate based on their size and density. All measurements were performed at rotational speed of 20,000 rpm and injection volume of 100 µL.

The results give high resolution particle size distributions, where particles sized between 0.1 µm and 1.0 µm are resolved, showing differences for different durations of sonication.

DSC Data

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LD and DCS were used as qualitative methods to assess the effectiveness of the acoustic processing in deagglomerating the particles. The two methods provided complementary information on the size distribution of the particles, the former being useful to assess deagglomeration of large particle agglomerates upon processing, while the latter describing the monodisperse particle population as well as the low coordination number agglomerates.

Despite the level of complexity, it was still possible to use the LD and DCS methods to observe relative changes to the samples upon different processing conditions.

Highlights of the Paper
  • Controlled inertial cavitation produced reproducible particle deagglomeration.
  • The inertial cavitation dose did not affect the spiky morphology of the particles.
  • Surface chemical analysis confirmed the loading of the particles with plasmid.
  • Thorough analysis was achieved through complementary particle characterisation methods.
About the Surface Technology Group

The Surface Technology group at NPL develop quantitative chemical methods for the measurement of high value products. NPL’s world-leading surface technology research has helped industry to use innovative products with confidence, having developed more efficient catalysts, improved the delivery of drugs and supported the development of graphene. Their expertise is based upon the underpinning scientific research they perform to support innovation, trade and industrial competitiveness.

About the Ultrasound and Underwater Acoustic Group

The Ultrasound and Underwater Acoustic group at NPL is leader in establishing measurement standardisation that today underpins the safe and effective application of medical and industrial ultrasound globally. This includes the development and exploitation of measurement devices and standards in industrial ultrasonics, particularly in high power ultrasound applications such as advanced pharmaceutical and food manufacturing, cleaning, and environmental remediation.

About the Biometrology Group

The Biometrology group at NPL is developing and using cutting-edge measurement tools and methods to apply expanding knowledge of biological processes to help create new treatments and diagnostics, as well as make current ones more effective. The group also work with industry to help translate innovation into applications in sectors ranging from biotechnology and drug development to agriculture and smart materials.

About NPL

NPL is the UK’s National Metrology Institute, providing the measurement capability that underpins the UK’s prosperity and quality of life.

From new antibiotics to tackle resistance and more effective cancer treatments, to secure quantum communications and superfast 5G, technological advances must be built on a foundation of reliable measurement to succeed. Building on over a century’s worth of expertise, our science, engineering and technology provides this foundation. We save lives, protect the environment and enable citizens to feel safe and secure, as well as support international trade and commercial innovation. As a national laboratory, our advice is always impartial and independent, meaning consumers, investors, policymakers and entrepreneurs can always rely on the work we do.

Based in Teddington, south-west London, NPL employs over 600 scientists. NPL also has regional bases across the UK, including at the University of Surrey, the University of Strathclyde, the University of Cambridge and the University of Huddersfield’s 3M Buckley Innovation Centre.

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