In Vitro Biological Properties of Cyclodextrin-Based Polymers: Interaction with Human Serum Albumin, Red Blood Cells and Bacteria

Abstract

The aim of this work was to investigate the physico-chemical and biological properties of cyclodextrin-based polymers by the example of interaction with human serum albumin, erythrocytes, and bacteria to understand the prospects of their application as drug delivery systems. We synthesized polymers based on one of cyclodextrin derivatives with nonpolar (-CH3) or polar (-CH2CH(OH)CH3) substituents by crosslinking with 1,6-hexamethylene diisocyanate or succinic anhydride. The polymers form particles with an average size of ~200 nm in the aqueous solutions; their structures were confirmed by FTIR and 1H NMR. Cyclodextrin derivatives and their polymers did not affect the secondary structure content of human serum albumin, which might mean a mild effect on the structural and functional properties of the main blood plasma protein. Polymers extract drug molecules from albumin + drug complex by 8–10%, which was demonstrated using ibuprofen and bromophenol blue as model bioactive molecules for site I and site II in protein; thus, the nanoparticles might slightly change the drug’s pharmacokinetics. Using the hemolysis test, we found that polymers interact with red blood cells and can be assigned to non-hemolytic and slightly hemolytic groups as biocompatible materials, which are safe for in vivo use. The cyclodextrins and their polymers did not extract proteins from bacterial cell walls and did not demonstrate any antibacterial activity against Gram-positive and Gram-negative strains. Thus, the cyclodextrin-based polymers possess variable properties depending on the substituent in the monomer and linker type; demonstrated biocompatibility, biodegradability, and negligible toxicity that opens up prospects for their application in biomedicine and ecology.