Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Researchers Develop ‘Onion’ Vesicles for Drug Delivery

Published: Wednesday, June 11, 2014
Last Updated: Wednesday, June 11, 2014
Bookmark and Share
University of Pennsylvania researchers have shown that dendrimer-based vesicles self-assemble with concentric layers of membranes, much like an onion.

One of the defining features of cells is their membranes. Each cell’s repository of DNA and protein-making machinery must be kept stable and secure from invaders and toxins. Scientists have attempted to replicate these properties, but, despite decades of research, even the most basic membrane structures, known as vesicles, still face many problems when made in the lab. They are difficult to make at consistent sizes and lack the stability of their biological counterparts.

Now, University of Pennsylvania researchers have shown that a certain kind of dendrimer, a molecule that features tree-like branches, offers a simple way of creating vesicles and tailoring their diameter and thickness. Moreover, these dendrimer-based vesicles self-assemble with concentric layers of membranes, much like an onion.

By altering the concentration of the dendrimers suspended within, the researchers have shown that they can control the number of layers, and thus the diameter of the vesicle, when the solution is injected in water. Such a structure opens up possibilities of releasing drugs over longer periods of time, with a new dose in each layer, or even putting a cocktail of drugs in different layers so each is released in sequence.

The study was led by professor Virgil Percec, of the Department of Chemistry in Penn’s School of Arts & Sciences. Also contributing to the study were members of Percec’s lab, Shaodong Zhang, Hao-Jan Sun, Andrew D. Hughes, Ralph-Olivier Moussodia and Annabelle Bertin, as well as professor Paul Heiney of theDepartment of Physics and Astronomy. They collaborated with researchers at the University of Delaware and Temple University.   

Their study was published in Proceedings of the National Academy of Sciences.

Cell membranes are made of two layers of molecules, each of which has a head that is attracted to water and a tail that is repelled by it. These bilayer membranes self-assemble so that the hydrophilic heads of the molecules of both layers are on the exterior, facing the water that is in the cell’s environment as well as the water encapsulated inside.  

For decades, scientists have been trying to replicate the most basic form of this arrangement, known as a vesicle, in the lab. Stripping out the additional proteins and sugars that cells naturally have in their membranes leaves just a double-walled bubble that can be stuffed with drugs or other useful content.

“The problem,” Percec said, “is that once you remove the proteins and the other elements of a real biological membrane, they are unstable and don't last for a long time. It's also hard to control their permeability and their polydispersity, which is how close together in size they are. The methodologies for producing them are also complicated and expensive.”

Research in this field has thus been focused on finding new chemistries to replace the fatty molecules that normally make up a vesicle’s bilayer.

The Percec group’s breakthrough came in 2010, when they started making vesicles using a class of molecules called amphiphilic Janus dendrimers.

Like the Roman god Janus, these molecules have two faces. Each face has tree-like branches instead of the head and tail found in the molecules that make up biological membranes found in nature. But like those molecules, these dendrimers are amphiphilic, meaning that one face’s branches is hydrophilic and the other is hydrophobic.

In 2010, Percec and his colleagues found the smallest possible amphiphilic Janus dendrimer. Dissolving those molecules in an alcohol solution and injecting them into water, the researchers found that they formed stable, evenly sized vesicles.

Not all cells are content with just a single bilayer, however. Some biological systems, such as gram-negative bacteria and the myelin sheaths that cover nerves, have multiple concentric bilayers. Having a model system with that arrangement could provide some fundamental insights to these real-world systems, and the added stability of extra layers of padding would be a useful trait in clinical applications. However, methods for producing vesicles with multiple bilayers remained elusive.  

“The only way it has been achieved in the past was through a complicated mechanical process, which was a dead end,” Percec said. “This was not a viable option for mass-producing multilayered vesicles, but, with our library of amphiphilic Janus dendrimers, we were lucky to find some molecules that have in their chemicals instructions needed to self-assemble into these very beautiful structures.”

By testing different dendrimers with different organic solvents, the research team found they could produce these onion-like vesicles and control the number of layers they contained. By changing the concentration of the dendrimers in the solvent, they could produce vesicles with as many as 20 layers when that solution was introduced to water. And because the layers are consistently spaced, the team could control the overall size of the vesicles by predicting the number of layers they could contain.       

To actually see the multilayered structure of their vesicles, the researchers used a technique known as cryogenic transmission electron microscopy, or CryoTEM. This technique can take pictures of objects at the nanoscale floating in aqueous solution. To keep the fluid-floating vesicles in frame, the team flash-froze the sample, locking them in amorphous ice that was free of damaging ice crystals.

With the vesicles characterized, a host of clinical applications are possible. One of the more enticing is encapsulating drugs in these vesicles. Many drugs are not water-soluble, so they need to be packaged with some other chemistry to allow them to flow through the bloodstream. The additional stability of multiple bilayers makes these onion vesicles an attractive option, and their unique structure opens the door to next generation nanomedicine.

“If you want to deliver a single drug over the course of 20 days,” Perce said, “you could think about putting one dose of the drug in each layer and have it released over time. Or you might put one drug in the first layer, another drug in the second and so on. Being able to control the diameter of the vesicles may also have clinical uses; target cells might only accept vesicles of a certain size.”

Further Information
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 2,800+ scientific posters on ePosters
  • More Than 4,000+ 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 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.

Related Content

Penn Engineering Team Showcases ‘Eye-on-a-Chip’ Technology
These small plastic chips contain microfluidic channels, carefully designed so that human cells can grow in them in a way that simulates the three-dimensional environments they would normally inhabit in the body.
Thursday, November 19, 2015
How Different Treatments for Crohn's Effect the Microbiome
Different treatments for Crohn's disease in children affects their gut microbes in distinct ways, which has implications for future development of microbial-targeted therapies for these patients, according to a study led by researchers from the Perelman School of Medicine at the University of Pennsylvania.
Friday, October 16, 2015
Profiling Non-Protein-Coding RNAs
Growing insights about a significant, yet poorly understood, part of the genome – the “dark matter of DNA” -- have fundamentally changed the way scientists approach the study of diseases.
Wednesday, October 14, 2015
New Target for Preventing Breast Cancer Relapses
A surprising, paradoxical relationship between a tumor suppressor molecule and an oncogene may be the key to explaining and working around how breast cancer tumor cells become desensitized to a common cancer drug, found researchers at the Perelman School of Medicine at the University of Pennsylvania.
Wednesday, October 14, 2015
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Friday, October 09, 2015
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
Thursday, October 08, 2015
MYC Oncogene Disrupts Cancers Rhythm
Findings inform time-dependent treatment for reducing side effects and increasing effectiveness of cancer medications.
Monday, September 21, 2015
Genes' Found that Play Major Role in Skin and Organ Development
Disruptions of splicing proteins cause facial, skin, organ defects in young mice.
Thursday, September 17, 2015
Viral Product That Promotes Immune Defense Against RSV Identified
A new study has identified a subset of viral products that are responsible for eliciting a strong immune response against RSV in people who become infected.
Wednesday, September 09, 2015
Synthetic DNA Vaccine Against MERS Shows Promise
A novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle East Respiratory Syndrome (MERS) coronavirus in animal species.
Friday, August 21, 2015
Cell Aging Slowed by Putting Brakes on Noisy Transcription
Experiments in yeast hint at ways to extend life of some human cells.
Monday, August 03, 2015
Disrupting Cells’ ‘Powerhouses’ Can Lead to Tumor Growth
University of Pennsylvania researchers find that mitochondrial defects have a key role in a cells becoming cancerous.
Monday, July 13, 2015
New Tracking Method Yields Insights into Mitochondrial Dynamics
Scientists from the University of Pennsylvania have devised a powerful new technique that enables the tracking of every mitochondrion as it moves within a cell.
Thursday, July 02, 2015
Classification of Gene Mutations in Neuroblastoma
Penn Medicine and CHOP experts define riskier mutations in neuroblastoma, setting stage for clinical trial.
Tuesday, November 11, 2014
Potential Therapy for Myasthenia Gravis
Penn study demonstrates efficacy of potential therapy for autoimmune disorder of muscle weakness.
Wednesday, October 08, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos