One of the most promising discoveries to protect the potency of heat labile drugs was announced last month by researchers at Tufts University School of Engineering: silk. These findings, published in the Proceedings of the National Academy of Sciences, demonstrate that the potency of vaccines and other drugs can be maintained without the need for refrigeration by stabilizing them in a silk protein made from silkworm cocoons. The pharmaceutical-infused silk matrices can be made in a variety of forms such as microneedles, microvesicles and films that allow the non-refrigerated drugs to be stored in a single device for months at a time before administration with essentially no potency degradation. To date, the research team hasn’t found any pharmaceutical that it is not able to stabilize.

The function of proteins found in most vaccines, biologicals and many other drugs depends on maintaining the structural integrity of long chains of amino acids that are folded into specific shapes. At elevated temperatures or in the presence of water such as high humidity, these chains tend to break and unfold, then clump together, rendering them inactive. What the study shows is that the purified silk, which is composed of interlocked crystalline sheets, is highly resistant to changes in moisture and temperature. The silk matrix traps and immobilizes the biomolecules and stabilizes their structures and keeps from denaturing by inhibiting their ability to unfold while protecting them from moisture, like nanococoons.

Dr. David L. Kaplan at Tufts University, who has been researching silk for more than two decades, led the work. The study was funded by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), the National Eye Institute (NEI) and the National Institute of Dental and Craniofacial Research (NIDCR).

Here’s how they did it: they started with silkworm cocoons, the raw material in nearly all silk production. They boiled the cocoons in a solution of sodium carbonate to separate a protein called fibroin, which is the one they want, from one called sericin, which they do not. The dissolved, purified silk protein was put in a salt solution, creating a new silk-based film, then mixed with a preservative and live measles, mumps and rubella (MMR) vaccine and two antibiotics (penicillin and tetracycline) and freeze-dried. MMR vaccine is unstable outside of refrigeration and quickly loses potency above the recommended storage temperature of 2 to 8° C. Penicillin and tetracycline also break down quickly when unrefrigerated. The researchers report that immobilizing the MMR vaccine in the silk film greatly enhanced its stability. Even after storage at 45° C for six months, the vaccine retained nearly 85% of its potency. Typically, the MMR vaccine would rapidly lose all its potency under those temperature conditions.

Immobilizing antibiotics in silk greatly increased their stability, too. Tetracycline lost only 20% of its activity when stored in silk at temperatures as high as 60° C for four weeks. These conditions would normally eliminate all its activity. Penicillin lost no detectable efficacy when stored in silk at 60° C for 30 days. Storage of the drug under those conditions typically brings a 20% loss in activity. The silk’s structure also excludes some water, enhancing its preservative qualities.

All vaccines are sensitive to heat (as are most biological drugs), and refrigeration is expensive, accounting for up to 80% of the cost of some drug products. It is estimated that nearly half of all global vaccines are lost due to temperature abuse resulting from breakdowns in the cold chain. Even within industrialized nations, loss of drug efficacy at body temperature is a serious problem for advanced drug delivery systems such as implantable drug-coated devices. The positive impact this technology may have on the supply chain, and ultimately the patient, is astounding.

Although silk is already approved by the FDA for some medical applications, Dr. Kaplan’s concept is far from becoming a pharmaceutical reality.

But it is worth pursuing. The university has optimistically begun additional studies with other proteins, peptides and enzymes, stating that there’s no reason to believe that this technology couldn’t be universal and in some cases completely eliminate the need for cold-chain systems, greatly decreasing costs and enabling more widespread availability of these life-saving therapies.