|Both gravity and electrostatics affected the delivery of drugs via a rooted delivery vehicle.--Courtesy of ACS Macro Letters|
Controlling how and when a specific drug is released is a major facet of drug delivery research. And understanding the way cells and drugs interact in a very detailed way can enable vehicles to fine-tune their delivery and optimize treatment for a long time within the body.
Focusing on the delivery of cancer drugs, researchers at the University of Copenhagen and the Institut Laue-Langevin in France have found that gravity and electrostatics are two important factors at play between cell membranes and drug reservoirs. With these new findings, as published in the journal ACS Macro Letters, the scientists hope to create systems that deliver cancer drugs slowly and continuously.
Ultimately, the tiny "drug cabinets" could attach to the outsides of, for instance, cancer cells to deliver a dose of drugs there for a long period of time. The particles themselves are a combination of phospholipids and branched macromolecules called dendrimers. With this shape, they soak up and carry large quantities of a drug. And the team looked closely at how they interact with cell membranes.
Using highly detailed neutron reflectometry to study the surface of cells, they found that the drug-carrying particles, depending on the negative charge on the membrane, used their treelike branches to "root" into a cell, attaching the rest of the molecule to the surface. From there the vehicle would sit and deliver drugs unhindered. What's more, cancer cells tend to have a more negative charge than surrounding cells, so they would already have that affinity.
"Cancerous cells have an imbalance that gives them a different molecular composition and overall different physical properties to normal healthy cells," study author Marité Cárdenas said in a statement. "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."
And then there's the role that gravity plays: The scientists were surprised to find that the molecules only worked when they were above the cell. Although it's not completely understood why this was the case, the researchers suspect that density and buoyancy play a part, and they hope to use these characteristics in future studies to tailor the molecules for drug delivery.