RETRACTED: Stabilization of vaccines and antibiotics in silk and eliminating the cold chain

Abstract

Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent “cold chain” to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self-standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 °C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world.

Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement

“…Additional strategies may be used at the time of film formation to further control and extend the release profile while maintaining the electronic interface. Exposure of antibiotic-loaded silk to higher temperatures did not negatively affect antibiotic activity likely due to the stabilization properties of the silk on heat-labile compounds, as previously reported (25,26). Remotely controlled, resorbable therapeutic devices offer an expanded perspective for medical devices.…”

“…The ability to control and wirelessly address therapy, whether thermal or biochemical, can enable broad operating windows with greater penetration depth than comparable noninvasive approaches. The results reported here focused on ampicillin release; however, approaches for broader applications in wireless drug release (ranging from for small to large molecules entrained in silk) can be pursued based on this approach, even above body temperature (26). This would provide opportunities for externally controllable, therapeutic medical electronic devices that provide therapy-on-demand, followed by device resorption in the body.…”

“…The cast-and-peel process was used, as previously reported (23). All samples were treated to be water insoluble through a vapor annealing process (16,17), which also helped to stabilize the drug within the crystallized silk matrix (24)(25)(26). Fig.…”

The use of silk-based devices for fracture fixation

“…After 4 and 8 week time points in vivo, there was early resorption of the silk screw. Future material iterations may involve the incorporation of bioactive compounds such as BMP-2 to promote bone ingrowth or antibiotics to prevent infection [19][20][21][22][23]32,33 . Such factors can be used to modulate healing and promote remodelling of bone.…”

Beyond antigens and adjuvants: formulating future vaccines

“…126, 128, 129, and Figure 2B). A particularly interesting example is the encapsulation of vaccine antigens within silk protein-based microneedles, as silk protein has been shown to thermostabilize vaccines in a dried state (130), and silk matrices can be designed to release vaccines with extended kinetics in the skin, promoting T cell and humoral responses following vaccination (128). A second approach that is promising, particularly for the development of therapeutic vaccines, is the formulation of antigens and danger signals together within porous PLGA polymer sponges, which are implanted into the skin.…”