a-, P-and y-cyclodextrins are cyclic hexamers, heptamers, and octamers of glucose, respectively, and thus are hydrophilic; nevertheless, they have the ability to solubilize lipids through the formation of molecular inclusion complexes. The volume of lipophilic space involved in the solubilization process increases with the number of glucose units in the cyclodextrin molecule and, consequently, cyclodextrins were found to have different effects on human erythrocytes: (a) in the induction of shape change from discocyte to spherocyte the potency was observed to be a > y, but with P-cyclodextrin hemolysis occurred before the change was complete; (b) in the increase of fluorescence intensity of 1 -anilinonaphthalene-8-sulfonate in cyclodextrin-pretreated membranes, the observed potency was / 3 9 y > a; (c) in the release of potassium and hemoglobin, the potency was P > a > y. The potencies of cyclodextrin for solubilizing various components of erythrocytes were a > P 9 y for phospholipids, P 9 y > a for cholesterol and $-y > a for proteins. The sohbilizdtion potencies were derived from concentration/ final-effect curves. The above processes occurred without entry of solubilizer into the membrane, since (a) p-]cyclodextrin did not bind to erythrocytes and (b) cyclodextrins did not enter the cholesterol monolayer. A study of the [3H]cholesterol in erythrocytes indicated that P-cyclodextrin extracted this lipid from membrane into a new compartment located in the aqueous phase which could equilibrate rapidly with additional erythrocytes. Therefore, the effects of cyclodextrins differ from those of detergents which first incorporate themselves into membranes then extract membrane components into supramolecular micelles.a-, P-and y-cyclodextrins are cyclic oligomers of glucose consisting of six, seven, and eight D-glucopyranose units, respectively, linked by a-glycosidic bonds. The number of these units determines the dimension of the torus-shaped hydrophobic cavity in which guest molecules of SUitdbk size and low polarity can be accomodated in rapidly established equilibria [I].The solubilization of lipophilic compounds by cyclodextrins has many uses in the biomedical field. Thus, solubilization with cyclodextrins of acyl coenzymes A was used in the study of fatty acid synthetase [2], in the partial replacement of serum in cell culture [3] and in assisting organisms to metabolize toxic lipophiles [4]. Cyclodextrins were also widely used both in oral and parenteral formulations of drugs [S, 61. The dissolution of lipids by cyclodextrins may be of use in the study of cell membranes and as an alternative to the use of detergents. The possibility to introduce cyclodextrins as a research tool in membrdne studies and the necessity to gather additional data in support of parenteral use of cyclodextrins led us to investigate the interaction of all three cyclodextrins with human erythrocytes. Previously, hemolysis by cyclodextrins and their methyl derivatives was investigated [7, 81. In this study, a broader investigation was m...

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The pharmaceutical usefulness of natural, crystalline cyclodextrins can be improved by chemical conversions into water-soluble, amorphous mixtures of their derivatives. Reaction of beta-cyclodextrin with 2-chloroethanol, 3-chloropropanol, isobutylene oxide, or iodoacetamide yielded the title compounds. Distributions of the substitution degree were close to symmetrical and relatively narrow. The average substitution degrees increased with the amount of alkylating reagent used in the preparation. The number of components (half-width of distribution) increased with increasing average substitution degree. Further, distributions of the substitution degree were measured in glucose derivatives after hydrolysis of 2-hydroxyethyl, 2-hydroxypropyl, and 2-hydroxyisobutyl-beta-cyclodextrin. The results show an uneven distribution of substituents around the cyclodextrins, suggesting that growth of oligoglycol side chains and/or clustering of substituents on one glucose residue occurs.

The water-insoluble aluminium salt of beta-cyclodextrin sulphate (Al.beta-CyD-Sul) was used as a stabilizer and sustained-release carrier for recombinant human basic fibroblast growth factor (bFGF). An adsorbate of bFGF with Al.beta-CyD-Sul was prepared by incubating the protein with a suspension of Al.beta-CyD-Sul in water. The mitogenic activity of bFGF released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamster (BHK-21), was almost comparable with that of the intact bFGF. Al.beta-CyD-Sul significantly protected bFGF from proteolytic degradation by pepsin and alpha-chymotrypsin, compared with the water-soluble sodium salt. The in-vitro release of bFGF from the adsorbate was sustained in proportion to a rise in the ratio of Al.beta-CyD-Sul to the protein in the adsorbate. Of the bFGF preparations evaluated, the adsorbate of bFGF with Al.beta-CyD-Sul, when given subcutaneously to the rat, showed the most prominent increase in the formation of granulation tissues, due to the stabilization and slow-release of the mitogen. The limited data presented here suggest that the adsorbate of bFGF with Al.beta-CyD-Sul has a potent therapeutic efficacy for wound healing, and may be applicable to oral protein formulations for the treatment of intestinal mucosal erosions.

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