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Triggered Drug Release

Conventional methods of drug administration such as tablets or intravenous injection typically distribute a drug throughout the body. This may be undesirable, however, in the case of drugs which show poor uptake in certain types of tissue and/or produce unwanted side effects.

The aim of the research being carried out in BUBBL is to develop systems which enable drugs to be encapsulated, targeted to a specific region and released “on demand” in response to an external stimulus, for example exposure to ultrasound. Such systems provide not only a means of controlling the drug concentration and reducing the risk of harmful side-effects, but also control over treatment location and timing.

See also The Oxford Centre for Drug Delivery Devices (OxCD3).

Vehicle Design & Fabrication

One of the key areas of research is the design and fabrication of stimuli responsive vehicles for drug delivery at the nanoscale and microscale. These include: engineered microbubbles, thermally and/or acoustically sensitive liposomes, polymeric capsules, sonosensitive nanoparticles and stabilized nanoemulsions.

A variety of manufacturing techniques are available in the laboratory for fabricating these vehicles, for example:

  • Microfluidics
  • Electrospraying
  • Spray drying
  • Freeze drying
  • Ultrasonic emulsification
  • Templating methods
  • Extrusion
  • Thin film hydration

Targeting Strategies

Magnetic MicrobubblesIn addition to encapsulating the drug, drug carriers can also be engineered to enable them to be concentrated in a target region. Strategies include:

  • Controlling the particle size distribution to exploit biological uptake mechanisms such as the enhanced permeability and retention (EPR) effect exhibited by certain types of tumour.
  • Incorporating magnetic nanoparticles to enable vehicles to be manipulated in vivo using and externally applied magnetic field.
  • Attaching targeting ligands to the vehicle surface to facilitate binding to target cells.
  • Incorporating acoustically active components and/or conjugating with microbubbles to exploit acoustic radiation force.

See also enhanced drug delivery.

Release Mechanisms

Release of the drug may be induced by exposing the vehicles to various external stimuli. The majority of the research currently being conducted in BUBBL is focused on the use of ultrasound to trigger release through:

  • Generation of heat to activate thermally sensitive carriers.
  • Generation of cavitation to physically disrupt carriers.
  • Mechanical oscillation of acoustically active vehicles.

See also enhanced drug delivery.

Other methods are also being investigated including:

  • Photosensitivity through the inclusion of gold nanoparticles
  • Sensitivity to certain chemical species/tissue environments
  • Charge sensitivity

The presence of stimuli responsive components may also be exploited to generate a signal detectable outside the body that can be utilized for monitoring of drug delivery.

For further details please see our publications pages.