Effect of surfactant on 5-aminolevulinic acid uptake and PpIX generation in human cholangiocarcinoma cell

Eur J Pharm Biopharm. 2012 Feb;80(2):453-8. doi: 10.1016/j.ejpb.2011.10.008. Epub 2011 Oct 18.

Abstract

Photodynamic therapy (PDT) is a palliative therapy and has been used to cure cholangiocarcinoma (CC), which has a poor prognosis and limited available curative therapy. PDT was shown to improve the median survival time of advanced-stage patients. Recently, 5-aminolevulinic acid (ALA) has been used as a pro-photosensitizer, which can be transferred to intercellular protoporphyrin IX (PpIX), which is a strong photosensitizer, via the heme pathway. The main limitation of using ALA in PDT is the hydrophilic properties of ALA, which results in low cellular uptake. In this study, non-ionic surfactants, pluronic F68 (PF68) and Tween 80 (TW80), were used to address this limitation. The human CC cell line, HuCC-T1, was cotreated with ALA and different concentrations of surfactants for 4h. The effect of surfactants was evaluated by monitoring the uptake of ALA, the fluorescence intensity of PpIX, and the cell survival rate after suitable light irradiation. Cotreatment with the surfactant resulted in an increased intracellular ALA level, PpIX formation, and phototoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / pharmacokinetics
  • Aminolevulinic Acid / pharmacology*
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / drug effects
  • Bile Ducts, Intrahepatic / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / pathology
  • Excipients / chemistry
  • Humans
  • Photochemotherapy / methods
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / pharmacology*
  • Poloxamer / chemistry
  • Polysorbates / chemistry
  • Protoporphyrins / metabolism
  • Surface-Active Agents / chemistry*

Substances

  • Excipients
  • Photosensitizing Agents
  • Polysorbates
  • Protoporphyrins
  • Surface-Active Agents
  • Poloxamer
  • Aminolevulinic Acid
  • protoporphyrin IX