Most of us have probably received vaccines and antibiotics at some point in our lives, and while they may have seemed to work like magic at the time, medical professionals’ precise understanding of the drugs’ mechanisms of action enables their use as the primary tools for fighting infection. Vaccines are made out of pieces of “dead” viruses or bacteria, and when administered, these particles train the body to recognize and attack similar foreign invaders. Medical personnel typically administer vaccines to patients in at-risk populations as preventive measures against viral infections, such as the measles, the mumps, and rubella (recall the dreaded MMR shot). Conversely, medical personnel turn to antibiotics to fight a bacterial infection once it has already begun. Antibiotics are typically composed of much smaller molecules than are vaccines. These small molecules directly attack bacteria, interfering with cellular processes the bacteria needs to grow and reproduce (and cause a nasty infection).
Figure 1: An colorized transmission electron micrograph of measles (yellow) and the SV Rubeola viruses (blue). Image Courtesy of: Reuters/Newscom/Handout <http://uk.reuters.com/article/2009/08/25/us-measles-vaccine-idUKTRE57O48T20090825>
While both vaccines and antibiotics play crucial roles in effective healthcare, their therapeutic efficacy is highly dependent on their storage in controlled cold and moisture-free environments. As such, their production, distribution and use requires a “cold chain” – a distribution network designed to carefully maintain the necessary cold temperatures during transport, storage, and handling of these sensitive biological compounds. The financial and logistical demands of the cold chain are heavy and particularly problematic in areas with developing infrastructure (roads, electricity supply, etc.). In fact, the World Health Organization estimates that the cold chain constitutes 80% of the financial cost of vaccination, and that gaps in the cold chain result in loss of close to half of all vaccines worldwide.
Professor David Kaplan, Ph.D., and his research colleagues at Tufts University have recently developed a method for stabilizing highly sensitive vaccines and antibodies even at high temperatures (60°C or 140°F) for long periods of time (over 6 months). Their method consists of encapsulating the drug molecules in a film of proteins made from silk, and it holds the promise to transform global drug distribution.
So . . .What Are Silk Films?
Bombyx mori (silkworms) secrete silk composed of two different types of protein that together make the resilient material constructing their cocoons. Of the two proteins, fibroin at the center of the silk strand is responsible for its tensile strength while sericin on the exterior of the strand is responsible for its stickiness and adhesive abilities (Figure 1). When silk is harvested from B. mori, it is typically processed so that only the fibroin – a long protein chain consisting of both hydrophobic (greasy or water-fearing) and hydrophilic (water-loving) regions – remains. The internal dichotomy of interspersed hydrophobic and hydrophilic regions allows the strands of silk fibroin to pack very tightly against each other (similar to the way droplets of oil bunch together when you put them in water) to form strong films interspersed with tiny crystalline pockets where the hydrophilic regions meet. When the silk is processed in a solution that also contains biological materials, such as vaccine particles or antibiotic small molecules, it can encapsulate these materials inside the crystalline pockets, protecting them from all external perturbation. [5,6]
Figure 2: Strands of silk fibroin from the Bombyx mori cocoon. Image Courtesy of: Keene, E. (2008) Entangled Silk Fibers. Cornell Center of Materials Research, Cornell University Dept Materials Science & Engineering <http://www.ccmr.cornell.edu/facilities/contestimages/Winners08Jan/keene.html>
Silk films are attractive materials for biomedical applications due not only to their durability under environmental and mechanical stress, but also to their compatibility with biological systems. In fact, silk fibroin has already been used in sutures and arterial stents, and the human body can break it down in a slow and controlled fashion to yield non-toxic degradation products. Particularly since they’re already considered safe in the human body, with the recent discovery that silk films can encapsulate biomolecules, the application of silk films as drug-delivery agents has become a booming area of research.
How Do Silk Films Stabilize Vaccines and Antibiotics?
To understand how silk films can stabilize biomolecules like vaccines and antibiotics, it is first important to understand how these biomolecules typically break down.
Larger biomolecules, like those in vaccines, can actually denature (or unfold) and aggregate when they are heated up, just like how an egg congeals when you cook it. When they are encapsulated in the silk films, however, these molecules are packed very tightly in miniscule spaces. This packing is so tight that the silk-film cavity actually holds the molecule in its active folded form, simply because the pocket does not allow enough space for unfolding to occur.
Smaller biomolecules, like most antibiotics, are more typically degraded by chemical reactions with water, oxygen, and light. When the small biomolecules are encapsulated in the silk film cavities, however, the offending reactants are excluded, and the small molecule remains protected from any external agents as long as the silk film remains intact.
In both cases, the active drugs are released as the silk film is slowly degraded by enzymes in the body.
The Kaplan group tested the stabilization that silk films afforded to the MMR (measles, mumps, rubella) vaccine as well as the antibiotics penicillin and tetracycline. They prepared the medications both in their typical solutions and in these novel silk films, and then stored the parallel samples for over six months at multiple temperatures ranging from 4°C (40°F, the temperature of a standard refrigerator) to 25°C (77°F, room temperature in an air-conditioned building) to 60°C (140°F, the temperature inside a car on a hot day). They checked on the samples periodically and measured how well the medications could combat bacterial cultures of their targeted pathogens. In all cases, the silk film-encapsulated medications remained potent for far longer than the solution-based samples, especially at elevated temperatures. 
For example, it took less than two weeks for a solution of the antibiotic tetracycline stored at 60°C (140°F) to completely loose its ability to combat bacteria. When tetracycline is wrapped in silk, however, it retains 80% of its activity against bacterial pathogens even after four weeks at the same temperature! 
Where Is This Headed Next?
While further studies are necessary to determine the optimal conditions for storing silk film-encapsulated medications and to evaluate appropriate methods for administering these new formulations to complex organisms (eventually humans), their successes thus far inspire incredible hope. Silk-encapsulation could completely revolutionize the way the world’s most sensitive medications are handled and distributed, thereby eliminating the need for the burdensome “cold chain” and bringing valuable medical resources to the developing areas that need them most. These advances could dramatically reduce the cost of vaccination programs and improve the quality of life for millions of individuals worldwide.
Rose Kennedy is a graduate student in the Department of Chemistry and Chemical Biology at Harvard University.
Omenetto, F; Kaplan, D. L. (2010) From silk cocoon to medical miracle. Sci. Am. 303:76–77.
Egan, K. (2012) Vaccine and antibiotics stabilized so refrigeration is not needed. NIH News. <http://www.nih.gov/news/health/jul2012/nibib-09.htm>
Lockwood, D. (2012) Silk Film Acts As Vaccine Preservative. C&EN <http://cen.acs.org/articles/90/web/2012/07/Silk-Film-Acts-Vaccine-Preservative.html>
Yong, E. (2012) Silk Cages Preserve Vaccines and Antibiotics for Months without Refrigeration. Discover Magazine <http://blogs.discovermagazine.com/notrocketscience/2012/07/10/silk-cages-preserve-vaccines-and-antibiotics-for-months-without-refrigeration/>
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 Public Health Agency of Canada (2007) National Vaccine Storage and Handling Guidelines for Immunization Providers. <http://www.phacaspc.gc.ca/publicat/2007/nvshglp-ldemv/index-eng.php>
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 Zhanga et al. (2012) Stabilization of vaccines and antibiotics in silk and eliminating the cold chain. Proc. Nat. Acad. Sci. 109: 11981–11986.
 Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32(8–9):991–1007