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.
Inelastic neutron scattering
Local anesthetics
Ropivacaine
Complexation
Bupivacaine
HP-?-cyclodextrin
Author
Murillo L. Martins
Niels Bohr Institute
Juergen Eckert
Los Alamos National Laboratory
University of South Florida
Henrik Jacobsen
University of Oxford
Niels Bohr Institute
Éverton C. dos Santos
Niels Bohr Institute
Norwegian University of Science and Technology (NTNU)
Rosanna Ignazzi
Niels Bohr Institute
Daniele Ribeiro de Araujo
Universidade Federal do ABC
Marie Claire Bellissent-Funel
University Paris-Saclay
Francesca Natali
National Research Council of Italy (CNR)
Institut Laue-Langevin
M. Koza
Institut Laue-Langevin
Aleksandar Matic
Chalmers, Physics, Condensed Matter Physics
Eneida de Paula
State University of Campinas
Heloisa N. Bordallo
Niels Bohr Institute
International Journal of Pharmaceutics
0378-5173 (ISSN) 1873-3476 (eISSN)
Vol. 524 1-2 397-406Driving Forces
Sustainable development
Areas of Advance
Building Futures (2010-2018)
Subject Categories
Condensed Matter Physics
DOI
10.1016/j.ijpharm.2017.03.051