Hydroxypropyl cyclodextrins: Potential synergism with carcinogens

The solubility of the lipophilic carcinogens benzo[a]pyrene and aflatoxin B-1 in water increases linearly and substantially with the concentration of hydroxypropyl beta-cyclodextrin present. Results of a kinetic study of naphthalene, a model for more potent carcinogens, indicate that the increase in the dissolution rate and in the transport through the aqueous phase into a nonpolar phase is on the same order of magnitude as the increase in solubility. Consequently, hydroxypropyl beta-cyclodextrin, when used in pharmaceutical formulations, has the potential to increase the absorption of carcinogens which enter the gastrointestinal tract either as food components or from air pollution through saliva. Only the above mechanism's simple proportionality needs be considered for estimating the increases in carcinogen absorption in the upper gastrointestinal tract and in the colon. In the presence of bile, however, additional factors are involved and the proportionality does not apply. Bile micelles, which themselves are effective solubilizers of lipophilic carcinogens, were disrupted by hydroxypropyl beta-cyclodextrin because of the formation of complexes with bile salts. Thus, in the presence of bile, two systems for delivery of carcinogens may coexist: that of cotransport with lipids and that of delivery through solubilization by hydroxypropyl beta-cyclodextrin.