Drug Delivery Through The Skin Made Easier Through Nanoemulsion Gels

Researchers from the Massachusetts Institute of Technology have developed a method to develop nanoemulsions or tiny liquid droplets suspended within another liquid. Their properties are similar to the mixture that forms oil-and-vinegar salad dressing is perturbed to create smaller droplets. This enables the emulsions to become relatively stable.

These chemical engineers devised a method in converting these liquid nanoemulsions to a gel when they attain body temperature (37 degrees Celsius). This opens opportunities to develop materials that deliver medicine when rubbed topically or injected into the body.

"The pharmaceutical industry is hugely interested in nanoemulsions as a way of delivering small molecule therapeutics. That could be topical, through ingestion, or by spraying into the nose, because once you start getting into the size range of hundreds of nanometers you can permeate much more effectively into the skin," says Patrick Doyle, the Robert T. Haslam Professor of Chemical Engineering and the senior author of the study.

The scientists published their findings in Nature Communications that showed that nanoemulsions they developed were stable for more than a year. They also demonstrated the usefulness for drug delivery in the body by integrating ibuprofen into the droplets.

Seyed Meysam Hashemnejad, a former MIT postdoc, is the first author of the study. Other authors include former postdoc Abu Zayed Badruddoza, L'Oréal senior scientist Brady Zarket, and former MIT summer research intern Carlos Ricardo Castaneda.

Adding energy is one of the easiest methods in creating an emulsion. This is done by shaking a salad dressing or using a homogenizer in breaking down milk's fat globules. Stability increases when there is a greater amount of energy, as well as the size of the droplets, gets smaller.

Nanoemulsions have more desirable properties in relation to drug delivery because they have a greater capacity to bring a larget amount of active ingredients due to their higher ratio of surface area to volume.

Surfactants, chemicals that have properties of detergents, catalyzes emulsion formation. The problem is that these surfactants are not approved by the FDA. Doyle and his team opted to choose two DFA-approved uncharged surfactants that are not skin irritants. Their team added a small amount of polyethylene glycol (PEG) which is a biocompatible polymer for drug delivery that can help in the formation of smaller droplets.

"With this approach, you don't have to put in much energy at all," Doyle says. "In fact, a slow stirring bar almost spontaneously creates these super small emulsions."

Active ingredients can be mixed into the oil phase before the emulsion is formed, so they end uploaded into the droplets of the emulsion.

The scientists added a step for the easy gel conversion of these nanoemulsions when they reach body temperature. This is obtained by integrating poloxamers, or heat-sensitive polymers which are already approved by the FDA in drugs and cosmetics.

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