Nanotechnology Laboratory

Nanoparticles and Nano-Scale Drug Delivery Systems

At the Centre for Vaccine Evaluation, research on nanoparticles and nano-scale drug delivery systems provides new information and tools for evaluating biologics that are being developed using nanotechnology.

Why We Study Nanotechnology and Products of Nanotechnology

Nanotechnology is the manipulation of material resulting in the production of particles generally small than 100nm. The resulting nanoparticles, due to their small size, may demonstrate altered physical, chemical and/or biological properties.

One of the most promising avenues for nanotechnology is in the medical field. Nanoparticles are currently being used, or are proposed for use, as an effective means for medical imaging as well as vaccine and drug delivery. As a result of the increased surface-to-volume ratio that nanoparticles display compared to the bulk form of the material, interactions between nanoparticles and biological systems are of special concern.

The human health effects of nanotechnology and nano-scale systems are research priorities for Health Canada. Of particular interest is the potential for enhanced interactions with proteins; either those found natively in the body or those administered with the nanoparticle as a therapeutic. Nanoparticle/protein interactions may cause alterations of protein conformation (shape) resulting in changes and/or loss of function or, if severe enough, recognition of the protein by the patient’s immune system as foreign.

How We Study Nanoparticles and Nano-Scale Drug Delivery Systems

The Centre for Vaccine Evaluation (CVE), is investigating techniques to better characterize and understand the properties of nano-scale drug delivery systems. Information gained from these studies will provide scientifically relevant experience, advice, and expertise in this critical and rapidly expanding field—both for the CVE and the regulatory decision-making process at Health Canada.

Specifically, research is focused on possible structural changes of proteins associated with nanoparticles and how these changes may influence therapeutic properties of either the protein or the nanoparticle delivery system.

Proteins or peptides associated with several nano-scale drug delivery systems are currently under development or approved for clinical use. These proteins may be an encapsulated therapeutic payload or they may be on the surface of the nanoparticle. Surface-associated proteins can allow for targeting of the nanoparticles to a specific tissue, cell type or entry point of a cell. CVE researchers study and characterize nanoparticles and nano-scale drug delivery systems in terms of size, surface charge and structure of surface associated proteins, using techniques such as submicron particle sizing, circular dichroism spectroscopy, and differential scanning calorimetry.

Scientists are currently studying a number of different nanoparticle drug delivery systems, including delivery systems based on lipid or protein nanoparticles. This research on nanoparticles and associated proteins provides valuable knowledge for:

  • Evaluating both nanoparticles and drug delivery systems based on nanoparticles, in terms of current regulations;
  • Developing or adapting existing techniques to further characterize nanoparticle drug delivery systems;
  • Predicting the effects of nanoparticle association on protein folding;
  • Understanding risks and mechanisms of adverse reactions due to structural changes in nanoparticle-associated proteins.

Concepts and Tools We Use to Study Nanoparticles and Nano-Scale Drug Delivery Systems

At the Centre for Vaccine Evaluation, scientists use the term “nanoparticles” to refer to particles that have at least one dimension sized between 1 and 100 nanometres. Nanoparticles include a wide range of particle types. Some occur naturally, while others are composed of chemically synthesized material. Their variable and unique properties make nanoparticles very useful as drug delivery systems.

Nano-scale drug delivery systems have the potential to offer many benefits over conventional delivery of therapies. These include:

  • Reducing toxicity or adverse effects by decreasing exposure of susceptible tissues;
  • Improving efficacy by:
    • Targeting disease sites;
    • Improving circulation lifetimes;
    • Controlling drug release;
    • Improving stability of active agents; and
    • Delivering compounds with poor solubility.
  • Enabling therapeutic activity of previously inactive agents;
  • Enabling alternative routes of drug administration and improving compliance by patients.

Examples of nano-scale drug delivery systems include dendrimers; lipid nanoparticles (liposomes); micelles; nanotubes; nanocages; nanoshells; polymeric drug carriers (conjugates); and protein-based delivery systems. Each of these systems differs in structure, composition and functional properties which make them attractive for particular applications.

Lipid nanoparticles are also known as liposomes. These artificial vesicles have one or more lipid bilayers surrounding an aqueous core. Lipid nanoparticles are one of the most widely used drug delivery systems, because they can encapsulate hydrophobic or hydrophilic drugs, show bio-compatibility and be functionally modified on their surface.

Protein-based delivery systems have been the focus of recent studies using albumin as a delivery system for other proteins or small molecule drugs. These albumin-based delivery systems showed improved pharmacokinetic profiles and tumour accumulation for the therapeutically active agent. Some albumin-based delivery systems are in late stage clinical studies or have been approved for use in the clinic.

Research Highlight 1: Characterization of Proteins That Are Associated with Liposome Nanoparticles

By formulating both small molecule drugs and biotherapeutics in nano-scale drug delivery systems (DDS), such as liposomes, researchers have seen an increase in the effectiveness of the therapeutic agent and a reduction in detrimental toxic adverse effects.

Studies show that efficacy can be further improved by targeting these systems at disease-specific cells or sites. Targeting is usually done by coupling ligands that recognize specific cell surface receptors or antigens to the exterior of the delivery systems. The targeting ligands can consist of antibodies, antibody fragments, peptides, small molecules or whole proteins.

The interactions between these targeting proteins and their associated nanoparticle, or between the nanoparticle and native proteins in the bloodstream are the focus of this research.

CVE Scientists are working to:

  • Adapt the techniques used for assessing the structure (secondary/tertiary) of proteins and peptides to the characterization of nanoparticle systems targeted with protein ligands;
  • Determine how various membrane properties and/or coupling technologies can result in structural changes of closely associated protein-targeting ligands;
  • Provide scientifically relevant advice to decision-makers to support Health Canada and the Biologics and Genetic Therapies Directorate (BGTD) in regulating the expected increase in nano-scale drug delivery systems.

For information about the lead scientist of this laboratory, please visit their  Directory of Scientists and Professionals profile.

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