Pharmaceutical Technology is pleased to recognize the winners of its Innovations in Pharma Science Awards. These awards honor
achievements in drug delivery, formulation, dosage-form manufacturing, pharmaceutical analysis, and the synthesis and manufacturing
of active ingredients. We received 20 nominations, based on original research or already published work, from companies around
the world. Fourteen members of our Editorial Advisory Board reviewed the nominations to determine the winners, showcased here.
Orally therapeutic proteins
Created by Lila Drittanti, Fernanda Sanchez, Thierry Guyon, Sophie Guillier, Mathilde Breton, and Manuel Vega
Nautilus Biotech SA (Evry, France)
(COURTESY OF NAUTILUS BIOTECH SA)
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Nautilus scientists adopted a strategy using protein engineering technology to create a "third generation" of protein drugs.
Using a patented proprietary systematic approach, the team designed specific point mutations to protect therapeutic protein
molecules from degradation by a wide range of proteases. In most cases, a single point mutation is enough to confer high resistance
to proteolysis even though biological activity is not affected; Nautilus used this fact to design variants that are highly
protected in vivo in skin, blood, and other fluids. These molecules degrade slower than the corresponding native proteins in the intestinal
tract and can be readily absorbed into the blood.
The proteins can be administered orally in the form of a lyophilized powder, which can be filled into gastro-resistant capsules
or used to make tablets. Nautilus developed a product pipeline around this innovation since 2002 that includes two orally
available versions of Belerofon, a novel form of interferon alpha, and Vitatropin, a single point mutation of native human
growth hormone. Both are designed for higher resistance to proteolysis in blood and other tissues. Nautilus is exploring additional
routes of delivery (sublingual, buccal, and nasal).
Nautilus' protease–resistant proteins are intrinsically bioavailable when delivered orally, thereby providing for better patient
compliance. The US Food and Drug Administration approved the company's investigational new drug application (IND) for the
oral administration of Belerofon in a Phase I clinical trial; an IND for Vitatropin is underway.
Intravail macromolecular absorption enhancers
Created by Dennis J. Pillion and Eli Meezan
Pharmacology & Toxicology, University of Alabama (Birmingham, AL) & Aegis Therapeutics (San Diego, CA)
(COURTESY OF AEGIS THERAPEUTICS)
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Peptide and protein drugs are among the most selective, potent, and effective drugs but their susceptibility to denaturation,
hydrolysis, and poor absorption, makes them unsuitable for oral administration. Professors Pillion and Meezan developed a
new class of patented alkylsaccharide transmucosal delivery-enhancement agents, collectively designated as "Intravail" absorption
enhancers. Intravail excipients provide unsurpassed intranasal, buccal, and oral bioavailabilities, often comparable to those
achieved by injection, for protein, peptide, and other macromolecular therapeutics. They circumvent the two primary limitations
of intranasal drug delivery (mucosal irritation and poor bioavailability) and offer more convenient, effective, and safe therapeutics.
Intravail excipients also provide controlled transient permeation of the mucosal barrier by both the paracellular and transcellular
routes. In intranasal administration, they speed onset of action. Nasal delivery also circumvents "first-pass" metabolism
in the liver. The technology has been demonstrated to work in human and animal studies with more than 20 drugs. Intravail
formulations can be administered using off-the-shelf metered nasal spray pumps.
