Articaine interaction with phospholipid bilayers

Author(s)

Prates, Erica Teixeira ^{[1, 2]} ; Rodrigues da Silva, Gustavo Henrique ^[3] ; Souza, Thais F. ^[3] ; Skaf, Munir S. ^[2] ; Pickholz, Monica ^{[4, 5]} ; de Paula, Eneida ^[3]

Affiliation

^[1] Oak Ridge Natl Lab, Biosci Div, POB 2009, Oak Ridge, TN 37830 - USA

^[2] Univ Estadual Campinas, Ctr Computat Engn & Sci, Inst Chem, UNICAMP, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, UNICAMP, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[4] Consejo Nacl Invest Cient & Tecn, IFIBA, RA-1428 Buenos Aires, DF - Argentina

^[5] Univ Buenos Aires, Fac Exact & Nat Sci, Dept Phys, RA-1428 Buenos Aires, DF - Argentina

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1222, DEC 15 2020.
• Web of Science Citations: 0

Abstract

Local anesthetics promote analgesia by interacting with excitable membranes. Articaine (ATC) has a unique composition among local anesthetics as it possesses a thiophene instead of the typical phenyl ring. Aiming to characterize the interaction of neutral articaine (nATC) with phospholipid membranes, we have employed a synergistic approach of experimental and computational techniques. Fluorescence measurements supported nATC partitioning into the membranes, since its intrinsic fluorescence anisotropy increased from 0.03 in water to 0.29 in the presence of egg phosphatidylcholine (EPC) liposomes, and the fluorescence of AHBA, a probe that monitors the water-membrane interface, was quenched by nATC. H-1 NMR experiments revealed changes in the chemical shifts of articaine and EPC hydrogens after partitioning, and shorter T-1 values of nATC hydrogens when inserted into the EPC vesicles. Contacts of nATC and the phospholipid polar head group were inferred from 2D-NOE. Taken together, these results indicate a superficial insertion of the nATC molecules inside EPC bilayers. This conclusion was confirmed by molecular dynamics simulations, which allowed the identification of the key interactions underlying the preferential location of nATC in the bilayer. Contrary to what is often stated (that articaine is a high lipophilic local anesthetic agent) our results place ATC among the hydrophilic ones, such as lidocaine, prilocaine, and mepivacaine, for which the water/membrane interface is the preferred location. (C) 2020 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/15174-5 - Development of functional lipid nanoparticles for the improvement of the anesthetic potency at inflamed tissues
• Grantee: Gustavo Henrique Rodrigues da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 07/02629-2 - Interactions of local anesthetics with phospholipid bilayers
• Grantee: Érica Teixeira Prates
• Support Opportunities: Scholarships in Brazil - Master