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Coarse grained simulations of local anesthetics encapsulated into a liposome.

We investigated the encapsulation of prilocaine (PLC), an aminoamide local anesthetic widely used in dentistry, into a small unilamellar liposome. We extended a recently developed coarse grained model to access the problem relevant time and length scales. Molecular dynamics (MD) simulations for diff... Full description

Journal Title: The journal of physical chemistry. B May 27, 2010, Vol.114(20), pp.7009-7015
Main Author: Pickholz, Mónica
Other Authors: Giupponi, Giovanni
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1520-5207 ; DOI: 1520-5207 ; DOI: 10.1021/jp909148n
Link: http://search.proquest.com/docview/733548517/?pq-origsite=primo
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title: Coarse grained simulations of local anesthetics encapsulated into a liposome.
format: Article
creator:
  • Pickholz, Mónica
  • Giupponi, Giovanni
subjects:
  • Anesthetics, Local–Administration & Dosage
  • Hydrogen-Ion Concentration–Chemistry
  • Hydrophobic and Hydrophilic Interactions–Chemistry
  • Liposomes–Chemistry
  • Molecular Dynamics Simulation–Administration & Dosage
  • Phosphatidylcholines–Chemistry
  • Prilocaine–Chemistry
  • Static Electricity–Chemistry
  • Anesthetics, Local
  • Liposomes
  • Phosphatidylcholines
  • Prilocaine
  • 1-Palmitoyl-2-Oleoylphosphatidylcholine
ispartof: The journal of physical chemistry. B, May 27, 2010, Vol.114(20), pp.7009-7015
description: We investigated the encapsulation of prilocaine (PLC), an aminoamide local anesthetic widely used in dentistry, into a small unilamellar liposome. We extended a recently developed coarse grained model to access the problem relevant time and length scales. Molecular dynamics (MD) simulations for different protonation states of the PLC captured important features of the PLC-vesicle interactions. We found that all neutral PLC molecules (nPLC) rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal density distribution, with nPLC molecules jumping between the internal and external vesicle monolayers. Protonated PLC molecules (pPLC) initially placed in water were instead only found on the external monolayer, with a high rate of exchange with the water phase and no access to the inner part of the liposome. Although electrostatic interaction between pPLC tails and oppositely charged lipid head groups is shown to be structured, hydrophobicity is the driving force of PLC drug absorption within the liposome. Our simulations also show that a major percentage of pPLC remains trapped within the interior water phase of the liposome when starting from a configuration with pPLC distributed within the lipid membrane. This suggests that at low pH liposome-PLC complexes and therefore drug efficacy can strongly depend on the preparation procedure.
language: eng
source:
identifier: E-ISSN: 1520-5207 ; DOI: 1520-5207 ; DOI: 10.1021/jp909148n
fulltext: no_fulltext
issn:
  • 15205207
  • 1520-5207
url: Link


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titleCoarse grained simulations of local anesthetics encapsulated into a liposome.
creatorPickholz, Mónica ; Giupponi, Giovanni
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subjectAnesthetics, Local–Administration & Dosage ; Hydrogen-Ion Concentration–Chemistry ; Hydrophobic and Hydrophilic Interactions–Chemistry ; Liposomes–Chemistry ; Molecular Dynamics Simulation–Administration & Dosage ; Phosphatidylcholines–Chemistry ; Prilocaine–Chemistry ; Static Electricity–Chemistry ; Anesthetics, Local ; Liposomes ; Phosphatidylcholines ; Prilocaine ; 1-Palmitoyl-2-Oleoylphosphatidylcholine
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descriptionWe investigated the encapsulation of prilocaine (PLC), an aminoamide local anesthetic widely used in dentistry, into a small unilamellar liposome. We extended a recently developed coarse grained model to access the problem relevant time and length scales. Molecular dynamics (MD) simulations for different protonation states of the PLC captured important features of the PLC-vesicle interactions. We found that all neutral PLC molecules (nPLC) rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal density distribution, with nPLC molecules jumping between the internal and external vesicle monolayers. Protonated PLC molecules (pPLC) initially placed in water were instead only found on the external monolayer, with a high rate of exchange with the water phase and no access to the inner part of the liposome. Although electrostatic interaction between pPLC tails and oppositely charged lipid head groups is shown to be structured, hydrophobicity is the driving force of PLC drug absorption within the liposome. Our simulations also show that a major percentage of pPLC remains trapped within the interior water phase of the liposome when starting from a configuration with pPLC distributed within the lipid membrane. This suggests that at low pH liposome-PLC complexes and therefore drug efficacy can strongly depend on the preparation procedure.
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