A revolutionary cure for protein instability
An ordered aqueous solution that mimics in-vivo
conditions may prove to be the cure for the instability
and reduced bioactivity that afflicts many protein-based
therapeutic formulations.
The development of protein-based pharmaceuticals is plagued by the "bio-monsters" of instability and reduced activity. Too many compounds cannot retain the protein's therapeutic properties long enough to benefit patients. We all know why. the protein's structural stability is undermined during the stringent purification required for vaccine and protein production, while thermostability issues make the compound vulnerable to damage from normal shipping temperatures.
The protein's biological clock begins ticking as soon as it debuts in the lab. The process of developing the therapeutic compound, sending it through the market distribution chain and preparing it for clearance in the patient is a race against time and nature. The industry's response has been to "stop the clock" by adding salts, sugars and other chemicals to the protein buffer solution, and by stabilising the protein through refrigeration/freezing. But these solutions have led to other
problems: degradation with reduced activity, undesirable side-effects from additives, painful injections due to a viscous solution, and the risk of tissue necrosis. And despite the costly stabilising efforts, the short-lived efficacy of suspensions has necessitated recalls of vaccine batches that fell below required potency levels.
Nanotechnology
The ideal answer would be to provide proteins with the environment that they need: an aqueous solution that mimics in-vivo conditions.
Do-Coop Technologies has investigated the unique properties of water together with the physical principles of in-vivo conditions. The result is a patented water-based nanotechnology branded as Neowater.
The unique molecular organisation of Neowater is derived from the interaction of the water, carbon dioxide and a minute amount of suspended insoluble nanoparticles arranged in clusters. Neowater harnesses the resulting surface effect to create structure within the water that is a superior environment for biological reactions.
Various studies have demonstrated that Neowater confers increased stability on proteins at elevated temperatures, as well as at 4°C. é-Galactosidase (é-gal), alkaline phosphatase (AP), restriction enzymes and Taq polymerase are just some of the proteins that showed greater stability at elevated temperatures in Neowater.
A Neowater environment not only induces thermostability in proteins, but the ordered aqueous environment also maintains and enhances protein bioactivity in pharmaceutical formulations. Moreover, the reduced need for additives lowers the viscosity of a Neowater-based formulation, improving vaccination procedures.
Study results
One evaluation study, conducted by Do-Coop Technologies and a leading European pharmaceutical company, examined the in-vitro binding activity of a commercial antibody when solvated with Neowater. The results demonstrated better binding affinity to an antigen, under various storage conditions and at elevated temperatures. Not only that, but exposure of the therapeutical agent to body temperature (37°C) showed a threefold increase in antigen binding capability, a result that strongly suggests that Neowater contributes to antibody activity under in-vivo conditions.
The revolutionary nature of Neowater in mirroring intracellular water allows
companies to accelerate and improve biological
reactions with minimal customisation, and enables
in-vivo responses closer to those of living organisms.
Companies can move from in-vitro development to
in-vivo delivery, and from early laboratory experiments
to late-stage studies in humans, more smoothly
and cost-effectively, with more confidence of
success. The achievement of all these benefits
simply by switching to a Neowater solution is
reality. It's just good science, good sense, and
good news for an industry plagued by faltering
R&D pipelines. And, who knows? Perhaps the
next protein rescued by Do-Coop's nanotechnology
will be the blockbuster drug of the decade
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