New research could ‘gel’ into something special for drug delivery

MIT scientists say that nanoemulsion gels offer a new way to deliver drugs through the skin

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CAMBRIDGE, Mass.—Not too many people like injections, and sometimes oral medications and other forms of delivery can pose problems as well. But while we may not be using “hypospray” devices for all the therapeutics like they seemed to do on the original “Star Trek” series, some recent work at the Massachusetts Institute of Technology (MIT) may offer a different way to get through the skin and into the system with medications—or at least improve injectable drugs when topical delivery still won’t work.
According to an article from the MIT News Office authored by Anne Trafton, “MIT chemical engineers have devised a new way to create very tiny droplets of one liquid suspended within another liquid, known as nanoemulsions. Such emulsions are similar to the mixture that forms when you shake an oil-and-vinegar salad dressing, but with much smaller droplets. Their tiny size allows them to remain stable for relatively long periods of time.”
MIT further reports that the work included finding a way to convert the liquid nanoemulsions to a gel when they reach body temperature, which could be useful for developing materials that can deliver medication when rubbed on the skin or injected into the body.
The study appeared in the June 21 issue of Nature Communications under the title “Thermoresponsive nanoemulsion-based gel synthesized through a low-energy process.”
“The pharmaceutical industry is hugely interested in nanoemulsions as a way of delivering small-molecule therapeutics. That could be topically, 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,” said Patrick Doyle, the Robert T. Haslam Professor of Chemical Engineering and the senior author of the study.
The MIT researchers created nanoemulsions that were stable for more than a year, and they were able to show that they could incorporate ibuprofen into the droplets.
As the MIT New Office article notes, detergent-like chemicals called surfactants can speed up the formation of emulsions, but many of the surfactants that have previously been used for creating nanoemulsions are not FDA-approved for use in humans.
As Doyle and his team wrote in the paper, “Thermoresponsive nanoemulsions find utility in applications ranging from food to pharmaceuticals to consumer products. Prior systems have found limited translation to applications due to cytotoxicity of the compositions and/or difficulties in scaling-up the process.”
Doyle and his team first started finding a way around these problems by identifying two surfactants that and were already FDA-approved as food or cosmetic additives and are uncharged, making them less likely to irritate the skin. In addition, they added a small amount of polyethylene glycol, a biocompatible polymer used for drug delivery that helps the solution to form droplets down to about 50 nanometers in diameter.
“Once they had developed a low-energy way to create nanoemulsions, using nontoxic ingredients, the researchers added a step that would allow the emulsions to be easily converted to gels when they reach body temperature,” Trafton wrote. “They achieved this by incorporating heat-sensitive polymers called poloxamers, or Pluronics, which are already FDA-approved and used in some drugs and cosmetics ... Pluronics contain three ‘blocks’ of polymers: The outer two regions are hydrophilic, while the middle region is slightly hydrophobic. At room temperature, these molecules dissolve in water but do not interact much with the droplets that form the emulsion. However, when heated, the hydrophobic regions attach to the droplets, forcing them to pack together more tightly and creating a jelly-like solid. This process happens within seconds of heating the emulsion to the necessary temperature.”
Doyle is now exploring ways to incorporate a variety of active pharmaceutical ingredients into this type of gel.

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