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Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations

Martins, Murillo L; Eckert, Juergen; Jacobsen, Henrik; dos Santos, Éverton C.; Ignazzi, Rosanna; de Araujo, Daniele Ribeiro; Bellissent-Funel, Marie Claire; Natali, Francesca; Koza, Michael Marek and Matic, Aleksander, et al. (2017) In International Journal of Pharmaceutics 524(1-2). p.397-406
Abstract

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-β-cyclodextrin (HP-β-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... (More)

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-β-cyclodextrin (HP-β-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-β-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-β-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.

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publication status
published
subject
keywords
Bupivacaine, Complexation, HP-β-cyclodextrin, Inelastic neutron scattering, Local anesthetics, Ropivacaine
in
International Journal of Pharmaceutics
volume
524
issue
1-2
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85017339498
  • wos:000401108500037
ISSN
0378-5173
DOI
10.1016/j.ijpharm.2017.03.051
language
English
LU publication?
yes
id
232501e6-545e-4726-9d41-dca24d257c23
date added to LUP
2017-04-26 11:14:49
date last changed
2018-01-07 12:00:51
@article{232501e6-545e-4726-9d41-dca24d257c23,
  abstract     = {<p>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, C<sub>18</sub>H<sub>28</sub>N<sub>2</sub>O) and ropivacaine (RVC, C<sub>17</sub>H<sub>26</sub>N<sub>2</sub>O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HP-β-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-β-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-β-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.</p>},
  author       = {Martins, Murillo L and Eckert, Juergen and Jacobsen, Henrik and dos Santos, Éverton C. and Ignazzi, Rosanna and de Araujo, Daniele Ribeiro and Bellissent-Funel, Marie Claire and Natali, Francesca and Koza, Michael Marek and Matic, Aleksander and de Paula, Eneida and Bordallo, Heloisa N.},
  issn         = {0378-5173},
  keyword      = {Bupivacaine,Complexation,HP-β-cyclodextrin,Inelastic neutron scattering,Local anesthetics,Ropivacaine},
  language     = {eng},
  month        = {05},
  number       = {1-2},
  pages        = {397--406},
  publisher    = {Elsevier},
  series       = {International Journal of Pharmaceutics},
  title        = {Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2017.03.051},
  volume       = {524},
  year         = {2017},
}