Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy

Abstract

Cyclodextrins (CDs) are a family of carrier molecules used to improve the pharmacokinetic parameters of therapeutic molecules. These cyclic oligosaccharides have medical and pharmaceutical applications by being able to form inclusion complexes with molecules that are poorly soluble in water. The benefits of these complexes are directed towards improving the chemical and biological properties-i.e., solubility, bioavailability, stability, non-toxicity and shelf life of drug molecules. Since the 1960s, the first inclusion complexes used in therapeutics were those with α-, β- and γ-CD, which proved their usefulness, but had certain degrees of particularly renal toxicity. Currently, to correct these deficiencies, β-CD derivatives are most frequently used, such as sulfobutylether-β-CD, hydroxypropyl-β-CD, etc. Therefore, it is of interest to bring to the attention of those interested the diversity of current and potential future clinical applications of inclusion complexes in veterinary medicine and to present the contribution of these inclusion complexes in improving drug efficacy. The most important biological activities of β-CD complexed molecules in the veterinary field are summarized in this short review.

Keywords: anti-inflammatory; antibiotic; antifungal; biological activity; cyclodextrin; inclusion complex; veterinary drugs.

Figure 1

The most common natural cyclodextrins: (a) α-cyclodextrin; (b) β-cyclodextrin; (c) γ-cyclodextrin; (d) the toroidal arrangement of the glucose monomers of cyclodextrins.

Figure 2

Schematic representation of the most common inclusion modalities: (a) complete inclusion of a hydrophobic molecule; (b) partial inclusion of only the hydrophobic part of an amphiphilic molecule; (c) inclusion into 2 CD molecules of a large hydrophobic molecule.

Figure 3

General structure of a β-CD derivative and some of the most commonly used substituents. The substituents (R) attached to the carbons in position 6 of the glucose monomers (located on the narrow rim of the toroid) are green, while those attached to carbons 2 or 3 (located on the large rim of the toroid) are red.