Effect of a β-cyclodextrin-epichlorohydrin copolymer on the solubility of cortexolone

Abstract

Cyclodextrins (CD) represent a class of natural cyclic oligosaccharides comprising 6(00, 7(1~), and 8(y) glucose residues linked by ct-l,4-glycoside bonds. The CD molecules have a hollow truncated cone configuration, with the intramolecular cavity (containing only CH groups and glycoside oxygens) being rather hydrophobic. This structures enables CD molecules to form inclusion complexes with various substances poorly soluble in water. Many drugs of steroidal nature are obtained by methods of microbiological transformation. However, the limited solubility of these compounds in water results in their transport to and from the cells proceeding at a slow rate. As is known, 13-CD additives to steroids in the course of transformation are capable of increasing the efficacy of bioconversion [ 1 ]. Unfortunately, the effect is limited by comparatively low solubility of 13-CD in water. For this reason, a promising way to intensification of the steroid bioconversion process consists in using well-soluble chemically modified 13-CD complexes. A possible method of obtaining such systems is the reaction of polycondensation between [3-CD and epichlorohydrin [2, 3]. A special feature of the resulting copolymers, in addition to their good solubility in water, is the ability to form complexes with large host molecules (greater than those typically involved in complexes with unmodified 13-CD) [2]. The purpose of this work was to study the possibility of intensifying the process of cortexolone bioconversion into hydrocortisone [4]. To solve this task, we have synthesized a water-soluble copolymer o f 13-CD with epichlorohydrin (IB-CD-ECH) and studied its interactions with the steroids of interest.