Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anesthetics

Int J Pharm. 2014 Oct 20;474(1-2):212-22. doi: 10.1016/j.ijpharm.2014.08.002. Epub 2014 Aug 7.

Abstract

The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes.

Keywords: Chemical permeation enhancers; Cytotoxicity; Dermal drug delivery; Molecular dynamic simulation; Ropivacaine; Tetracaine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Amides / administration & dosage
  • Amides / chemistry
  • Amides / pharmacology
  • Anesthetics, Local / administration & dosage*
  • Anesthetics, Local / chemistry
  • Anesthetics, Local / pharmacology
  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • HEK293 Cells
  • Humans
  • Lysine / administration & dosage
  • Lysine / chemistry*
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Permeability / drug effects
  • Ropivacaine
  • Skin / drug effects
  • Skin / metabolism*
  • Skin Absorption*
  • Surface-Active Agents / administration & dosage*
  • Surface-Active Agents / chemistry*
  • Swine
  • Tetracaine / administration & dosage
  • Tetracaine / chemistry
  • Tetracaine / pharmacology

Substances

  • Amides
  • Anesthetics, Local
  • Biocompatible Materials
  • Surface-Active Agents
  • Tetracaine
  • Ropivacaine
  • Lysine