X-Message-Number: 24291
Date: Tue, 22 Jun 2004 21:15:56 -0700 (PDT)
From: Doug Skrecky <>
Subject: Keeping Drugs Stable Without Refrigeration

A spoonful of sugar may help the medicine go down, but it may take only a
thin coating of freeze-dried sugar to keep insulin, vaccines and other
heat-sensitive, protein-based drugs working reliably even when stored at
room temperature and above. Widespread availability of stable,
room-temperature therapeutic proteins and vaccines would lower the cost
and increase the convenience of these drugs, and could dramatically
improve distribution in areas of developing nations where refrigeration
may be limited.

New measurements taken by National Institute of Standards and Technology
(NIST) scientists and published in the June edition of Biophysical
Journal show that rapidly solidified sugars preserve such proteins best
when they suppress tiny, molecular motions lasting a nanosecond or less.
NIST scientists Christopher Soles and Marcus Cicerone used instruments at
the NIST Center for Neutron Research to help them view nanoscale
molecular motions of sugar mixtures that were designed to encase
proteins. They found a striking correlation between sugar mixtures that
provide unusually good protein stabilization and a suppression of very
fast motions in the sugars.

Scientists have known for more than a decade that "glassy" sugars can
preserve medicines by encasing the proteins in a protective coating. The
NIST measurements show that tiny molecular "wiggling" that facilitates
protein degradation occurs at time and length scales smaller than once
thought to matter. They found that diluting sugars that become "glassy" at
a relatively high temperature with the right amount of glycerol formed a
stiffer material, further restricting the protein's movement. It's as
though the sugar glove is now made of cement instead of cloth, says
Cicerone

Biophys J. 2004 Jun;86(6):3836-45
Fast dynamics and stabilization of proteins: binary glasses of trehalose
and glycerol.
Cicerone MT, Soles CL.
Polymers Division, National Institute of Standards and Technology,
Gaithersburg, Maryland.
  We present elastic and inelastic incoherent neutron scattering data
from a series of trehalose glasses diluted with glycerol. A strong
correlation with recently published protein stability data in the same
series of glasses illustrates that the dynamics at Q >/= 0.71 A(-1) and
omega > 200 MHz are important to stabilization of horseradish peroxidase
and yeast alcohol dehydrogenase in these glasses. To the best of our
knowledge, this is the first direct evidence that enzyme stability in a
room temperature glass depends upon suppressing these short-length scale,
high-frequency dynamics within the glass. We briefly discuss the coupling
of protein motions to the local dynamics of the glass. Also, we show that
T(g) alone is not a good indicator for the protein stability in this
series of glasses; the glass that confers the maximum room-temperature
stability does not have the highest T(g).

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