Researchers at Tufts University School of Engineering have discovered a
way to maintain the potency of vaccines and other drugs -- that otherwise
require refrigeration -- for months and possibly years at temperatures above
110 degrees F, by stabilizing them in a silk protein made from silkworm cocoons.
Importantly, the
pharmaceutical-infused silk can be made in a variety of forms such as micro-needles,
micro-vesicles and films that allow the non-refrigerated drugs to be stored and
administered in a single device.
The Tufts findings address a
serious obstacle to the effective use of life-saving pharmaceuticals: keeping
them cold. Most vaccines, enzymes, and antibodies and many antibiotics and
other drugs require constant refrigeration from manufacture to delivery to
maintain their effectiveness.
International health experts
estimate that nearly half of all global vaccines are lost due to breakdowns in
the "cold chain." Even in industrialized nations, loss of drug
efficacy at body temperature is a serious problem for advanced pharmaceutical
delivery systems such as implantable drug-coated devices.
The research will be published
before print in the Proceedings of the National Academy of Sciences (PNAS)
Online Early Edition the week of July 9, 2012.
Tufts biomedical engineers led by
David L. Kaplan, Ph.D., found that silk stabilization preserved the efficacy of
the measles, mumps and rubella (MMR) vaccine, as well as penicillin and
tetracycline, at a wide range of temperatures (at least up to 60 degrees C or 140
F) significantly better than other options such as collagen encapsulants, dried
powders and solutions.
"Silk protein has a unique
structure and chemistry that makes it strong, resistant to moisture, stable at
extreme temperatures, and biocompatible, all of which make it very useful for
stabilizing antibiotics, vaccines and other drugs. The fact that we can also
make silk into micro-needles to deliver a vaccine is an enormous added
advantage that can potentially provide a lot of useful solutions to stabilization,
distribution and delivery," says Kaplan, who has been studying silk for
two decades.
Protein function depends on
chains of amino acids folding into specific shapes. At higher temperatures or
in the presence of water, the chains tend to unfold, then clump together, which
renders them inactive. Silk fibroin is composed of interlocked crystalline
sheets with numerous tiny hydrophobic pockets. The pockets trap and immobilize
bioactive biomolecules -- keeping them from unfolding -- and also protect them
from moisture. The end result is like enveloping a fragile material in a
nanoscale Bubble Wrap.
According to the paper’s first
author, Jeney Zhang, who is pursuing a Tufts doctorate in chemical and
biological engineering, silk stabilization has "the potential to
significantly change the way we store and deliver pharmaceuticals, especially
in the developing world."
Measles is one of the leading
killers of children worldwide. Without
refrigeration, the MMR vaccine rapidly loses potency. But after six months of
storage in freeze-dried silk films at body temperature (37 C) and at 113 F (45
C), all components of the vaccine retained approximately 85 percent of their
initial potency.
Silk-stabilized antibiotics also
retained high activity. Storage in silk films at body temperature resulted in
no activity loss for tetracycline, compared with an 80 percent loss within four
weeks of storage in solution. Even for films stored at 140 F (60 C),
tetracycline activity loss was only 10 percent after two weeks, compared with
100 percent loss after two weeks of storage in solution. No activity loss was
observed for penicillin stored in silk films at 60 C for 30 days; in contrast,
total activity loss was observed within 24 hours when penicillin was stored in
solution at the same temperature.
Silk stabilization also protected
the tetracycline against degradation by light, a benefit that the researchers
did not anticipate, according to co-author and research assistant professor
Bruce Panilaitis. Panilaitis earned his
Ph.D. in biology at Tufts Graduate School of Arts and Sciences before joining
Kaplan's lab in 2001 as a postdoctoral fellow.
So far, Panilaitis adds, the
researchers haven't found any pharmaceutical that they have been unable to
stabilize. This could be a "universal storage and handling system."
Additional authors on the paper
include Eleanor Pritchard, who earned her doctorate in biomedical engineering
at Tufts and is now a postdoctoral fellow at St. Jude Children’s Research
Hospital in Memphis; Xiao Hu, a biomedical engineering postdoctoral fellow who
will join Rowan University as an assistant professor in September; Thomas
Valentin, a biomedical engineering master's degree student; and Fiorenzo
Omenetto, Ph.D., professor of biomedical engineering.
The research was supported by a
grant from the National Institute of Biomedical Imaging and Bioengineering at
the National Institutes of Health. It builds on a significant body of work
previously published by Tufts biomedical engineers seeking to tap the potential
of silk for a wide range of applications. In December 2011 researchers from
Kaplan’s lab announced development of a silk-based micro-needle system able to
deliver precise amounts of drugs over time and without need for refrigeration.
Source: Tufts University
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