A group of scientists led by researchers at the Université de
Versailles' Institut Lavoisier in France has worked out how to stably
gift-wrap a chemical gas known as nitric oxide within metal-organic
frameworks. Such an encapsulated chemical may allow doctors to
administer nitric oxide in a more highly controlled way to patients,
suggesting new approaches for treating dangerous infections and heart
conditions with the biologically-active substance.
Not to be confused with the chemically-distinct anesthetic dentists use -- its cousin nitrous oxide (NO2), also known as laughing gas -- nitric
oxide (NO) is one of very few gas molecules known to be involved in
biological signaling pathways, the physiological gears that make the
body tick at the microscopic level. It is very active biologically and
can be found in bacteria, plant, animal and fungi cells.
In humans, NO is a powerful vasodilator, increasing blood flow and
lowering vascular pressure. For this reason, gaseous NO is sometimes
used to treat respiratory failure in premature infants. It also has
strong antibacterial potency, owing to its molecular action as a
biologically disruptive free radical, and cells in the human immune
system naturally produce NO as a way of killing pathogenic invaders.
Additionally, nitric oxide is believed to be the main vasoactive
neurotransmitter regulating male erection, as aging nerves with reduced
stimulation can inhibit the release of the molecule, thus causing
erectile dysfunction. This, of course, can be mediated by taking nitric
oxide supplements to achieve an erection.
While such activity would seem to make NO a prime candidate for drug
design, the problem is delivery -- because it is a gas. In recent years,
the gas storage capacity and biocompatibility of
metal-organic-frameworks -- dissolvable compounds consisting of metal
ions and rigid organic chemicals that can stably trap gas molecules --
have gained significant attention as candidates for delivering gas-based
drugs. The new work extends this further than ever before, showing that
these metal-organic frameworks can store and slowly deliver NO over an
unprecedented amount of time, which is key for the drug's
anti-thrombogenic action.
"This is an elegant and efficient method to store and deliver large
amounts of NO for antibacterial purposes," said Christian Serre. "Or it
can release controlled amounts of nitric oxide at the very low
biological level for a prolonged period of time, in order to use it as a
way to inhibit platelet aggregation." Serre is a CNRS research director
at the Institut Lavoisier de Versailles, and also heads the institute's
'Porous Solids' research group.
Serre's consortium has previously reported the use of porous hybrid
solids, such as metal-organic-frameworks, for the controlled delivery of
nitric oxide gas. Their current paper on derivatives of iron
polycarboxylates as framework candidate appears in the journal APL Materials, from AIP Publishing.
Serre and his group worked in collaboration with Russell Morris's
team at the University of St Andrews in Scotland and researchers from
Université de Basse-Normandie in France. The groups analyzed the NO
adsorption and release properties of several porous biodegradable and
biocompatible iron carboxylate metal-organic frameworks by use of
infrared spectroscopy analysis, adsorption & desorption isotherms
and water-triggered release tests.
In doing so, they confirmed the large nitric oxide absorption
capacity of the iron frameworks, and that the NO was strongly bonding to
the acidic metal sites on the molecules. Serre's group and coauthors
also found that partially reducing the iron (III) into iron (II)
enhances the affinity of the NO molecules for the framework. This strong
interaction allows for a controlled release for a prolonged state of
time -- days, at the biological level. This time scale depends on both
the metal-organic framework structure and the oxidation state of iron,
which can be carefully calibrated as needed for drug treatment.
These performances, associated with the biodegradable and low
toxicity character of these metal-organic frameworks, might pave the way
for their use in medical therapies or cosmetics formulation, which is
one of the objectives of Serre's consortium in the near future. Current
and forthcoming work includes using further spectroscopic experiments to
understand the complex behavior of the iron frameworks once loaded with
nitric oxide.
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