Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Century-old rule of chemistry overturned -- major implications for drug delivery

Abstract:
A new study by research chemists at the University of Warwick has challenged a century old rule of pharmacology that defined how quickly key chemicals can pass across cell walls. The new observations of the Warwick researchers suggest that the real transport rates could be up to a hundred times slower than predicted by the century old "Overton's Rule". This could have major implications for the development and testing of many future drugs.

Century-old rule of chemistry overturned -- major implications for drug delivery

UK | Posted on August 25th, 2008

Overton's rule says that the easier it is for a chemical to dissolve in a lipid (fat) the easier and faster it will be transported into a cell. The Rule was first outlined in the 1890s by Ernst Overton of the University of Zürich. He declared that substances that dissolve in lipids pass more easily into a cell than those that dissolve in water. He then set forth an equation that predicted how fast that diffusion would happen. One of the key parameters in that equation is K which defines the lipophilicity (oil-liking nature) of the chemical. The higher the value of K, the faster the predicted cell permeation rate. For over a century, medicinal chemists have used this relationship to shape their studies and clinical trials.

A team of electrochemists from the University of Warwick used a combination of a confocal microscope and an ultramicroelectrode to study what really happens when a chemical crosses a cell membrane. Advances in technology enabled them to position an ultramicroelectrode incrediblely close to the membrane boundary (roughly 20 microns away; ca. 1/3rd the thickness of a human hair) where it was used to generate a range of acids that should be able to diffuse relatively easily into a cell. These techniques allowed every step of the diffusion process to be directly examined. Previous studies had not been able to observe every step of the process and often required artificial stirring of the solutions.

The results stunned the researchers. While the acids did diffuse across a lipid membrane, they did so at rates that were diametrically opposite to the predictions of the Rule, i.e. the most lipophilic molecules were actually transported slowest. The researchers studied four acids (acetic, butanoic, valeric, and hexanoic) that had increasingly larger "acyl" (or carbon) chains. The longer the carbon chain, the easier the chemical dissolves in lipids and, therefore, according to Overton, the faster they should diffuse across a lipid membrane. In fact, the University of Warwick researchers observed that for these four acids the exact opposite is true: the easier it is for an acid to dissolve in a lipid, the slower it is transported across the membrane.

The research team will now use their technique to examine the diffusion into cells of a range of other chemicals. The lead researcher on the study from the University of Warwick, Professor Patrick Unwin, said:

"This was a surprising and exciting finding. Our direct observations appear to totally undermine a key rule that has withstood the test of time for over a century. We will now make observations with a range of other chemicals, and with other techniques, to further elucidate the molecular basis for our observations. Text books will have to be rewritten to revise a rule that has been relied on for over a century. Advanced techniques, such as the one we have developed, should give much clearer insight into the action of a wide range of drug molecules, which will be of significant interest to drug developers."

The research is published today, Wednesday 26th August, in the Proceedings of the National Academy of Sciences (PNAS) and is entitled "Quantitative visualization of passive transport across bilayer lipid membranes". The authors (all from the University of Warwick) are John M. A. Grime, Martin A. Edwards, Nicola C. Rudd and Professor Patrick R. Unwin. The research was funded by the UK's Engineering and Physical Sciences Research Council (EPSRC) and the University of Warwick's Postgraduate Research Fellowship Scheme. Two of the researchers - John Grime and Martin Edwards - are postgraduate students in Warwick's innovative Doctoral Training Centre on Molecular Organisation and Assembly in Cells (MOAC), which attracts graduates from the physical and mathematical sciences to tackle significant problems in the life sciences.

####

For more information, please click here

Contacts:
Professor Patrick Unwin

44-024-765-23264

Peter Dunn
Press and Media Relations Manager
University of Warwick
Tel: +44 (0)24 76 523708
mobile/cell +44 (0)7767 655860

Copyright © University of Warwick

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Northwestern researchers achieve unprecedented control of polymer grids: Materials could find applications in water purification, solar energy storage, body armor June 22nd, 2018

Nanobiotix Publishes Positive Phase 2/3 Data For Nanomedicine in Soft Tissue Cancer (Webcast June 22) June 22nd, 2018

Alzheimer's breakthrough: Brain metals that may drive disease progression revealed: In brains affected by Alzheimer's, researchers identify chemically reduced iron species, with mineral forms including a magnetic iron oxide June 22nd, 2018

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

Chemistry

Quantum Interference May Be Key to Smaller Insulators: Breakthrough could jumpstart further miniaturization of transistors June 6th, 2018

Density gradient ultracentrifugation for colloidal nanostructures separation and investigation June 5th, 2018

From Face Recognition to Phase Recognition: Neural Network Captures Atomic-Scale Rearrangements: Scientists use approach analogous to facial-recognition technology to track atomic-scale rearrangements relevant to phase changes, catalytic reactions, and more May 31st, 2018

Northwestern researchers predict materials to stabilize record-high capacity lithium-ion battery: Advancement could pave the way for less expensive, longer-lasting batteries for electric vehicles May 29th, 2018

Discoveries

Alzheimer's breakthrough: Brain metals that may drive disease progression revealed: In brains affected by Alzheimer's, researchers identify chemically reduced iron species, with mineral forms including a magnetic iron oxide June 22nd, 2018

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

Carbon nanotube optics poised to provide pathway to optical-based quantum cryptography and quantum computing: Researchers are exploring enhanced potential of carbon nanotubes for unique applications June 18th, 2018

Camouflaged nanoparticles used to deliver killer protein to cancer June 17th, 2018

Announcements

Northwestern researchers achieve unprecedented control of polymer grids: Materials could find applications in water purification, solar energy storage, body armor June 22nd, 2018

Nanobiotix Publishes Positive Phase 2/3 Data For Nanomedicine in Soft Tissue Cancer (Webcast June 22) June 22nd, 2018

Alzheimer's breakthrough: Brain metals that may drive disease progression revealed: In brains affected by Alzheimer's, researchers identify chemically reduced iron species, with mineral forms including a magnetic iron oxide June 22nd, 2018

Collaboration yields discovery of 12-sided silica cages June 20th, 2018

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project