SAFETY OF ORAL CYCLODEXTRINS - EFFECTS OF HYDROXYPROPYL CYCLODEXTRINS, CYCLODEXTRIN SULFATES AND CATIONIC CYCLODEXTRINS ON STEROID BALANCE IN RATS

Derivatives of beta-cyclodextrin differing in the length of a hydroxya lkyl substituent (CH2CH2OH, CH2CHOHCH3, CH2CHOHCH2CH2CH2CH3) or in the electrical charge of the substituents (SO4-, CH2CHOHCH2N(CH3)(3)(+)) and hydroxypropyl derivatives (CH2CHOHCH3) of alpha-, beta-, and gamma -cyclodextrin were compared, individually and in mixtures, as solubili zers of cholesterol. The most effective solubilizer proved to be hydro xypropyl derivatives of beta-cyclodextrin; beta-cyclodextrin sulfate ( SO4-) was practically devoid of solubilizing activity. Oral administra tion of these cyclodextrin derivatives, some of which are both nondegr adable and effective complexation agents for cholesterol and bile acid s, nevertheless did not affect the conversion of [C-14] acetic acid to [C-14]- cholesterol in rat under the same conditions when another bil e acid complexation agent, cholestyramine, increased that conversion. Thus, complexation of cholesterol and of bile acids by cyclodextrin de rivatives, which is a significant and well-defined phenomenon in vitro , seems to have limited importance in terms of excretion of cholestero l from the gastrointestinal tract. It is proposed that various untowar d effects observed after chronic large oral doses of hydroxypropyl bet a-cyclodextrin are administered are not caused by an increased excreti on of some vital lipophile or enzyme but are probably caused by solubi lization and increased absorption of toxic contaminants of the ingeste d food.