Leave it to a student to ask a really hard question! The difficulty of the question lies in fact that it is actually multiple questions. If we break this down, the following “sub” questions arise:

1. Are peptides adequately absorbed from the nasal cavity?

We already have a history to indicate a level of success and a promising future for nasal delivery of peptides. Examples of commercial products include calcitonin and desmopressin nasal sprays. In addition, continued research demonstrates the potential of intranasal insulin and other peptide drugs. A wide range of formulation approaches continue to show promise to further increase nasal bioavailability, including: permeation enhancers (lipids, pegylated peptides, liposomes), nanoparticulate techniques, and mucoadhesive microspheres). A study released by Drug and Market Development Publishing points out that that peptides represent a small but increasing number of drugs. In addition, the report (Peptides 2006: New Applications in Discovery, Manufacturing, and Therapeutics) points out that peptide drugs are being developed for an increasing wide range of indications that include allergy/asthma, arthritis, diabetes, cardiovascular , CNS diseases, inflammation, and others.

2. Are peptides effectively absorbed across the blood-brain barrier (BBB)?

With respect to Alzheimer’s disease, the blood-brain barrier presents a major challenge to treatment. As a result of its unique physiology, the BBB hinders the delivery of many potentially efficacious drugs to the brain. A number of techniques are being investigated for capability to improve transport across the BBB. Examples of techniques include: vasoactive substances such as bradykinin, carrier mediated transporters such as amino acids or glucose, liposomal formulations, and nanotechnology. Some therapeutic approaches in which nanotechnology is being applied for the therapeutic investigation of Alzheimer’s disease include neuroprotections against oxidative stress, anti-amyloid therapeutics, and neuroregeneration.

3. Do peptides demonstrate pharmacologic activity for the treatment of Alzheimer’s disease?

Peptide drugs are an area of focus for new drugs targeted for Alzheimer’s disease. From the drug-delivery perspective, modified peptide drugs may overcome some deficient pharmacological properties of native peptides. These modified peptides feature changes to natural amino acid sequence, backbone replacements, cyclic structures, or other modifications such as pegylation. Adessi et.al.,(2003) showed that a chemically modified 5-amino acid β-sheet breaker peptide (iAβ5p) demonstrated increased stability in vitro, a 10-fold higher in vivo half-life and good brain uptake compared with the parent iAβ5p in an animal model. Allon Therapeutics has completed a Phase IIa study of an intranasal neuroprotective peptide to enhance memory and cognitive function in patients with mild cognitive impairment, a precursor to Alzheimer’s disease.

In summary, the question reveals a good example where multidisciplinary research efforts work synergistically to yield medical advances. For example, major advances may be found where a novel peptide drug is delivered to the brain in a nanocarrier from a formulation optimized for nasal delivery.