Characterization of the Inclusion Mode of .BETA.-Cyclodextrin Sulfate and Its Effect on the Chlorpromazine-Induced Hemolysis of Rabbit Erythrocytes.

Abstract

The inclusion mode of beta-cyclodextrin sulfate (beta-CyD-sul) with a cationic drug, chlorpromazine, was investigated, and the effect of beta-CyD-sul on the hemolytic activity of chlorpromazine was compared with that of parent beta-CyD. The interaction of beta-CyD-sul with chlorpromazine was weaker than that of parent beta-CyD, probably because of the steric or electrostatic repulsion between anionic sulfate groups and hydrophobic phenothiazine moiety. Spectroscopic studies, including pH- and salt-effects, as well as thermodynamic parameters, suggested that both electrostatic and hydrophobic interactions are operative in the inclusion complexation of beta-CyD-sul with chlorpromazine. The inhibiting effect of parent beta-CyD on the chlorpromazine-induced hemolysis of rabbit erythrocytes was accounted for by the decreased fraction of free drug through the complexation. In the case of beta-CyD-sul, the hemolysis and binding of the drug to the erythrocyte membrane was higher than those estimated from the fraction of free drug, probably due to the increased hydrophobicity of the drug through the complexation. However, the chlorpromazine-induced shape change of the erythrocytes was significantly suppressed by beta-CyD-sul, and its inhibiting effect was greater than that of beta-CyD, because of the counterbalance of the opposite effects, i.e., internalization and externalization induced by chlorpromazine and beta-CyD-sul, respectively.

Design and Evaluation of Cyclodextrin-Based Drug Formulation

“…Branched CyDs, 23,24,[164][165][166] b-CyD sulphate [167][168][169] and sulfoalkyl ethers of CyDs 122) may be a new class of parenteral drug carriers because they are highly hydrophilic and less hemolytic than parent and other hydrophilic CyDs. When insulin solutions containing SBE4-b-CyD were injected into the dosal subcutaneous tissues of rats, the plasma immunoreactive insulin (IRI) level rapidly increased and maintained higher IRI levels for at least 8 h (Fig.…”

Comparative Effects of (SBE)7m‐β‐CD and HP‐β‐CD on the Stability of Two Anti‐neoplastic Agents, Melphalan and Carmustine

“…This decrease in intensity in the presence of the cyclodextrins is consistent with the exposure of the drug to a nonpolar environment. The differences could be due to either the fraction of melphalan bound 23,24 and/or differences in the properties of the site of binding. 25 Because the K 1:1 values for both cyclodextrins are essentially identical, the fraction of the free and bound melphalan and carmustine should be about the same for both cyclodextrins.…”

Isolation and characterization of β‐cyclodextrin sulfates by preparative gradient polyacrylamide gel electrophoresis, capillary electrophoresis and electrospray ionization—mass spectrometry

“…1) have been shown to have some of the same biological properties as heparin, including the ability to inhibit angiogenesis (new vessel growth) [ 11, inhibit complement activation [2], modify cell growth and exhibit antiviral activity [3]. P-Cyclodextrin sulfates have also been used as excipients to carry water-insoluble drugs [4]. The utility of cyclodextrin sulfates for these pharmaceutical applications is dependent on the degree of sulfate substitution.…”