Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations
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 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.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1563056
- Alternate Identifier(s):
- OSTI ID: 1413841; OSTI ID: 1543548
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- International Journal of Pharmaceutics
- Additional Journal Information:
- Journal Name: International Journal of Pharmaceutics Journal Volume: 524 Journal Issue: 1-2; Journal ID: ISSN 0378-5173
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Pharmacology & Pharmacy; Local anesthetics; Bupivacaine; Ropivacaine; HP-β-cyclodextrin; Complexation; Inelastic neutron scattering
Citation Formats
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, Matic, Aleksander, de Paula, Eneida, and Bordallo, Heloisa N. Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations. Netherlands: N. p., 2017.
Web. doi:10.1016/j.ijpharm.2017.03.051.
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, Matic, Aleksander, de Paula, Eneida, & Bordallo, Heloisa N. Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations. Netherlands. https://doi.org/10.1016/j.ijpharm.2017.03.051
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, Matic, Aleksander, de Paula, Eneida, and Bordallo, Heloisa N. Mon .
"Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations". Netherlands. https://doi.org/10.1016/j.ijpharm.2017.03.051.
@article{osti_1563056,
title = {Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations},
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.},
abstractNote = {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.},
doi = {10.1016/j.ijpharm.2017.03.051},
journal = {International Journal of Pharmaceutics},
number = 1-2,
volume = 524,
place = {Netherlands},
year = {Mon May 01 00:00:00 EDT 2017},
month = {Mon May 01 00:00:00 EDT 2017}
}
https://doi.org/10.1016/j.ijpharm.2017.03.051
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