Development and characterization of farnesol complexed in β- and hydroxypropyl-β-cyclodextrin and their antibacterial activity.

Abstract

Farnesol (FAR) belongs to terpenes group and is a sesquiterpene alcohol and a hydrophobic compound, which can be extracted from natural sources or obtained by organic chemical or biological synthesis. Recent advances in the field of nanotechnology allow the drawbacks of low drug solubility, which can improve the drug therapeutic index. Therefore, this study aimed to prepare the FAR inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) through freeze-drying method, proposing their physicochemical characterization, comparing their toxicity, and evaluating their in vitro antibacterial activity. Initially, physical mixture and freeze-dried inclusion complexes of FAR/β-CD and FAR/HP-β-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FTIR, PXRD, SEM, pH_PZC, and the complexation efficiency were performed by HPLC. In vivo toxicity assay was performed using Tenebrio molitor larvae to determine the LD50 and toxic dose of the samples. Also, it was proposed that the evaluation of the fluorescence suppression of Bovine Serum Albumin and the antibacterial activity. The complexation of FAR was evidenced with β-CD and HP-β-CD by the characterization techniques analyzed. The complexation efficiency of FAR/β-CD and FAR/HP-β-CD were 73,53 % and 74.12 %, respectively. The inclusion complexes demonstrated a reduction in toxicity, as evidenced by lower toxic and LD50 doses compared to the free FAR. The inclusion complexes induced conformational changes in BSA, suggesting that they reached the subdomains containing tryptophan residues. In terms of antibacterial activity, FAR/β-CD and FAR/HP-β-CD did not exhibit significant MIC results compared to free FAR, except for FAR/HP-β-CD against S. aureus ATCC 25923.