Translational research: the changing landscape of drug discovery.

Drug discovery represents the first step in the creation of new drugs, and takes place in academic institutions, biotech companies, and large pharmaceutical corporations. Until recently, these sectors have each operated independently with little collaboration between those at the forefront of discovery research and those with experience in developing drugs. With the rise of translational research these relationships are shifting and new hubs are emerging, as key players seek to pool the expertise necessary to generate new therapies by linking laboratory discoveries directly to unmet clinical needs.

Absorption of polyethylene glycol (PEG) polymers: the effect of PEG size on permeability.

Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55-20 kDa from the lung, since this system provides a reservoir that limits rapid diffusion of molecules away from the site of delivery and enables permeability over longer times to be examined.

The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics.

Conjugation of macromolecules to polyethylene glycol (PEG) has emerged recently as an effective strategy to alter the pharmacokinetic (PK) profiles of a variety of drugs, and thereby to improve their therapeutic potential. PEG conjugation increases retention of drugs in the circulation by protecting against enzymatic digestion, slowing filtration by the kidneys and reducing the generation of neutralizing antibodies. Often, PEGylation leads to a loss in binding affinity due to steric interference with the drug-target binding interaction.

The lungs as a portal of entry for systemic drug delivery.

The lung is naturally permeable to all small-molecule drugs studied and to many therapeutic peptides and proteins. Absorption can be estimated using a simple animal test, intratracheal instillation. Inhalation offers a noninvasive route for the delivery of peptides and proteins that otherwise must be injected.