HYDROXYPROPYL CYCLODEXTRINS - POTENTIAL SYNERGISM WITH CARCINOGENS

The solubility of the lipophilic carcinogens benzo[a]pyrene and aflato xin B-1 in water increases linearly and substantially with the concent ration of hydroxypropyl beta-cyclodextrin present. Results of a kineti c 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 magni tude as the increase in solubility. Consequently, hydroxypropyl beta-c yclodextrin, when used in pharmaceutical formulations, has the potenti al to increase the absorption of carcinogens which enter the gastroint estinal tract either as food components or from air pollution through saliva. Only the above mechanism's simple proportionality needs be con sidered for estimating the increases in carcinogen absorption in the u pper 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-cyclo dextrin because of the formation of complexes with bile salts. Thus, i n the presence of bile, two systems for delivery of carcinogens may co exist: that of cotransport with lipids and that of delivery through so lubilization by hydroxypropyl beta-cyclodextrin.