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.