title: Characterization, in Vivo Evaluation, and Molecular Modeling of Different Propofol-Cyclodextrin Complexes To Assess Their Drug Delivery Potential at the Blood-Brain Barrier Level.
abstract: In this study, we investigated the ability of the general anesthetic propofol (PR) to form inclusion complexes with modified β-cyclodextrins, including sulfobutylether-β-cyclodextrin (SBEβCD) and hydroxypropyl-β-cyclodextrin (HPβCD). The PR/SBEβCD and PR/HPβCD complexes were prepared and characterized, and the blood-brain barrier (BBB) permeation potential of the formulated PR was examined in vivo for the purpose of controlled drug delivery. The PR/SBEβCD complex was found to be more stable in solution with a minimal degradation constant of 0.25 h-1, a t1/2of 2.82 h, and a Kcof 5.19 × 103M-1and revealed higher BBB permeability rates compared with the reference substance (PR-LIPURO) considering the calculated brain-to-blood concentration ratio (logBB) values. Additionally, the diminished PR binding affinity to SBEβCD was confirmed in molecular dynamics simulations by a maximal Gibbs free energy of binding (ΔGbind= -18.44 kcal·mol-1), indicating the more rapid PR/SBEβCD dissociation. Overall, the results demonstrated that SBEβCD has the potential to be used as a prospective candidate for drug delivery vector development to improve the pharmacokinetic and pharmacodynamic properties of general anesthetic agents at the BBB level.
authors: Department of Anesthesia and Critical Care, University of Würzburg , 97080 Würzburg, Germany.
authors: Sergey
authors: S
authors: Shityakov
authors: Department of Biophysics, School of Medicine, Bahcesehir University , 34349 Istanbul, Turkey.
authors: Ramin Ekhteiari
authors: RE
authors: Salmas
authors: Department of Biophysics, School of Medicine, Bahcesehir University , 34349 Istanbul, Turkey.
authors: Serdar
authors: S
authors: Durdagi
authors: Department of Anesthesia and Critical Care, University of Würzburg , 97080 Würzburg, Germany.
authors: Ellaine
authors: E
authors: Salvador
authors: Sapiotec Ltd. , 97078 Würzburg, Germany.
authors: Katalin
authors: K
authors: Pápai
authors: Universidad Católica San Antonio de Murcia (UCAM) , 30107 Guadalupe, Spain.
authors: Maria Josefa
authors: MJ
authors: Yáñez-Gascón
authors: Universidad Católica San Antonio de Murcia (UCAM) , 30107 Guadalupe, Spain.
authors: Horacio
authors: H
authors: Pérez-Sánchez
authors: CycloLab Cyclodextrin Research & Development Laboratory Ltd. , H-1097 Budapest, Hungary.
authors: István
authors: I
authors: Puskás
authors: Department of Anesthesia and Critical Care, University of Würzburg , 97080 Würzburg, Germany.|Sapiotec Ltd. , 97078 Würzburg, Germany.
authors: Norbert
authors: N
authors: Roewer
authors: Department of Anesthesia and Critical Care, University of Würzburg , 97080 Würzburg, Germany.
authors: Carola
authors: C
authors: Förster
authors: Department of Anesthesia and Critical Care, University of Würzburg , 97080 Würzburg, Germany.|Sapiotec Ltd. , 97078 Würzburg, Germany.
authors: Jens-Albert
authors: JA
authors: Broscheit
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D056004:Molecular Dynamics Simulation; D015742:Propofol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D018686:Anesthetics, Intravenous; D003692:Delayed-Action Preparations; D047392:beta-Cyclodextrins; C083507:propofol hydroxypropyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; D015742:Propofol