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Computer Simulations for Improved Liposome Design

By LabMedica International staff writers
Posted on 25 Oct 2015
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Image: A liposome, stabilized by anchoring its membrane to a solid cord with polymeric tethers, could provide a more stable carrier for nanoparticles (Photo courtesy of ACS Nano: http://pubs.acs.org/doi/10.1021/acsnano.5b03439)
Image: A liposome, stabilized by anchoring its membrane to a solid cord with polymeric tethers, could provide a more stable carrier for nanoparticles (Photo courtesy of ACS Nano: http://pubs.acs.org/doi/10.1021/acsnano.5b03439)
The extensive use of computer simulations has enabled researchers to design an improved class of liposomes for use in targeted delivery of toxic chemotherapeutic agents.

Liposomes are vesicles comprising a hydrophilic core enclosed by a membrane that contains mostly phospholipids and sometimes one or more types of proteins. The lipid membrane shields any material that it contains (such as a drug or nucleic acid) from interaction with the blood, while the proteins recognize and interact with complementary proteins on the membrane of a diseased or dysfunctional cell.

The primary weakness of the liposome delivery method is linked to the relative fragility of the vesicle. Studies of this model of delivery have shown that in many cases less than 10% of the drugs transported by liposomes are delivered to tumor cells. Often, the liposome breaks open before it reaches its target, and the drug is absorbed into the body's organs, including the liver and spleen, resulting in toxic side effects.

Investigators at Carnegie Mellon University (Pittsburgh, PA, USA) and colleagues at the University of California, Davis (USA) and the Colorado School of Mines (Golden, CO, USA) developed computer simulations that enabled them to propose designs for more stable liposomes.

In a paper published in the September 18, 2015, online edition of the journal ACS Nano they proposed the design for a nanoparticle carrier that combined three existing motifs into a single construct: a liposome that was stabilized by anchoring it to an enclosed solid core via extended polymeric tethers that were chemically grafted to the core and physisorb into the surrounding lipid membrane.

They suggested that such a design would exhibit several enticing properties, among them: (i) the anchoring would stabilize the liposome against a variety of external stresses, while preserving an aqueous compartment between core and membrane; (ii) the interplay of design parameters such as polymer length or grafting density would enforce strong constraints on nanoparticle size and hence ensures a high degree of uniformity; and (iii) the physical and chemical characteristics of the individual constituents would equip the construct with numerous functionalities that could be exploited in many ways.

"Even with current forms of targeted drug delivery, treatments like chemotherapy are still very brutal. We wanted to see how we could make targeted drug delivery better," said senior author Dr. Markus Deserno, professor of physics at Carnegie Mellon University.

Related Links:
Carnegie Mellon University
University of California, Davis
Colorado School of Mines


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