Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations
Journal article, 2017
Since potential changes in the dynamics and mobility of drugs upon complexation for delivery may affect their ultimate efficacy, we have investigated the dynamics of two local anesthetic molecules, bupivacaine (BVC, C18H28N2O) and ropivacaine (RVC, C17H26N2O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-?-cyclodextrin (HP-?-CD). The study was carried out by neutron scattering spectroscopy, along with thermal analysis, and density functional theory computation. Mean square displacements suggest that RVC may be less flexible in crystalline form than BVC, but both molecules exhibit very similar dynamics when confined in HP-?-CD. The use of vibrational analysis by density functional theory (DFT) made possible the identification of molecular modes that are most affected in both molecules by insertion into HP-?-CD, namely those of the piperidine rings and methyl groups. Nonetheless, the somewhat greater structure in the vibrational spectrum at room temperature of complexed RVC than that of BVC, suggests that the effects of complexation are more severe for the latter. This unique approach to the molecular level study of encapsulated drugs should lead to deeper understanding of their mobility and the respective release dynamics.
Local anesthetics
HP-?-cyclodextrin
Bupivacaine
Inelastic neutron scattering
Complexation
Ropivacaine
Author
Murillo L. Martins
Niels Bohr Institute
Juergen Eckert
Los Alamos National Laboratory
University of South Florida Tampa
Henrik Jacobsen
Niels Bohr Institute
University of Oxford
Éverton C. dos Santos
Niels Bohr Institute
Norges Teknisk-Naturvitenskapelige Universitet
Rosanna Ignazzi
Niels Bohr Institute
Daniele Ribeiro de Araujo
Universidade Federal do ABC
Marie Claire Bellissent-Funel
Universite Paris Saclay
Francesca Natali
Research National Council (CNR-IOM)
Institut Laue-Langevin
M. Koza
Institut Laue-Langevin
Aleksandar Matic
Chalmers, Physics, Condensed Matter Physics
Eneida de Paula
Universidade Estadual de Campinas
Heloisa N. Bordallo
Niels Bohr Institute
International Journal of Pharmaceutics
0378-5173 (ISSN)
Vol. 524 1-2 397-406Driving Forces
Sustainable development
Areas of Advance
Building Futures (2010-2018)
Subject Categories (SSIF 2011)
Condensed Matter Physics
DOI
10.1016/j.ijpharm.2017.03.051