Corporate Banner
Satellite Banner
Medicinal Chemistry
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

World’s Tiniest Drug Cabinets could be Attached to Cancerous Cells for Long Term Treatment

Published: Wednesday, January 15, 2014
Last Updated: Wednesday, January 15, 2014
Bookmark and Share
Reservoirs of pharmaceuticals could be manufactured to bind specifically to infected tissue such as cancer cells for slow, concentrated delivery of drug treatments.

The findings, from the University of Copenhagen and the Institut Laue-Langevin (ILL), came as a result of neutron reflectometry studies at the world’s leading neutron source in Grenoble, France. They could provide a way to reduce dosages and the frequency of injections administered to patients undergoing a wide variety of treatments, as well as minimising side effects of over-dosing.

The attachment of reservoirs of therapeutic drugs to cell membranes for slow diffusion and continuous delivery inside the cells is a major aim in drug R&D. A promising candidate for packaging and carrying concoctions of drugs is a group of self-assembled liquid crystalline particles. Composed of fatty molecules – phospholipids - and tree-like macromolecules called dendrimers, the particles form spontaneously and have the capacity to soak up and carry large quantities of drug molecules for prolonged diffusion. They are also known for their ability to bind to cellular membranes.

The first treatments using such particles are close to market through products incorporating a similar formulation called Cubosomes (cubic phase nanoparticles). Developed and commercialized by Swedish start-up Camarus Ab, its FluidCrystal® nanoparticles promise months of drug delivery from a single injection and the possibility of tuning the delivery to intervals of anything from once a day to once a month. However, a key requirement for optimal application of these formulations is a detailed understanding of how they interact with cellular membranes.

This was the focus of a collaboration between Dr Marité Cárdenas (Copenhagen) and Dr Richard Campbell and Dr Erik Watkins (ILL). In this experiment the team used neutrons to analyse the interaction of the liquid crystalline particles with a model cellular membrane whilst varying two parameters:

• Gravity – to see how the interaction changed if the aggregates attacked the cell membrane from below as opposed to above
• Electrostatics – to see how the balance between positive and negative charges of the aggregate and membrane affect the interaction

The team utilised a technique known as neutron reflectometry whereby beams of neutrons are skimmed off a surface. The reflectivity is measured and used to infer detailed information about the surface, including the thickness, detailed structure and composition of any layers beneath. These experiments were carried out on the FIGARO instrument at the ILL in Grenoble which offers unique reflection up vs. down modes that allowed the team to examine the top and bottom surfaces, alternating the samples on a two hourly basis during a 30 hour sampling period.

The interaction of the liquid crystalline particles with the membrane was shown to be driven by the charge on the model cell membrane. Subtle changes in the degree of negative charge on the membrane encouraged the tree-like dendrimer molecules to penetrate, allowing the rest of the molecule to bind to the surface, forming an attached reservoir. The sensitivity of the interaction to small changes in charge suggests that simple adjustments to the proportion of charged lipids and macromolecules could optimise this attachment. In the future this characteristic could also provide a mechanism to focus the treatment at targeted cells such as those infected by cancer, which are thought to be more negatively charge than healthy cells.

"Cancerous cells have an imbalance that gives them a different molecular composition and overall different physical properties to normal healthy cells”, explains Dr Cardenas. “Whilst all cells are negative, cancerous cells tend to be more negatively charged than healthy ones due to a different composition of fatty molecules on their surface. This is a property that we believe could be exploited in future research into delivery mechanisms involving the attachment of lamellar liquid crystalline particles. Our next step is to introduce the drug itself into the reservoirs and make sure it can move across the membrane. This work paves the way for cell tests and clinical trials in the future exploiting our methodology”

In terms of gravitational effects, the analysis also showed that aggregates interacted more strongly with membranes when located above the sample. Similar effects caused by differences in density and buoyancy of solutions are already exploited in some stomach treatments and the researchers would encourage future studies into how gravitational effects could be used to optimise these interactions for drug delivery.

The research was published in ACS Macro Letters.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Experimental Drug Cancels Effect from Key Intellectual Disability Gene
A University of Wisconsin—Madison researcher who studies the most common genetic intellectual disability has used an experimental drug to reverse — in mice — damage from the mutation that causes the syndrome.
Doubling Down on Dengue
HMS researchers have discovered two ways a compound blocks dengue virus.
Reprogramming Scorpion Venom
‘Twist of nature’ neutralizes toxin.
Tailoring a Suit for Tumor-Penetrating Cancer Meds
For more than a decade, biomedical researchers have been looking for better ways to deliver cancer-killing medication directly to tumors in the body.
Resurrecting an Abandoned Drug
Previously discarded drug shows promise in helping human cells in a lab dish fight off two different viruses.
Safer, Cheaper, Greener and More Efficient System for Organic Synthesis
The new medium not only supports organic synthesis it also produces considerably higher yields of product than pure organic solvents.
Fighting Prostate Cancer
Identifying the most promising compounds which can be used as medications for prostate cancer.
Collaboration to Develop Cancer Therapeutics
Major license agreement with Merck, enabled by Blavatnik Biomedical Accelerator, aims to develop therapy for most common form of acute leukemia.
Faster UVA Molecular Analysis Technology
There are people in the world – chemical engineers, astronomers, national defense scientists investigating an explosion – who need to know just what something is made of, down to the molecular level.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!