The purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na(2)EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro. The effective permeability coefficient (P(eff)) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 +/- 0.44)* 10-5, while in the presence of sodium caprate (0.5%) a P(eff) of (9.58 +/- 1.82)*10-5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na(2)EDTA > poly-L-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na2EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4 degrees C compared to 37 degrees C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport. The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease.