Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies

The objective of the present investigation was to study the ability of sulfobutylether--cyclodextrin (SBECD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBECD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (P-app). In addition, SEV binding affinity to SBECD was confirmed by a minimal Gibbs free energy of binding (G(bind)) value of -1.727 +/- 0.042 kcalmol(-1) and an average binding constant (K-b) of 53.66 +/- 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.