Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline) formulation: An improved penetration and biological effect of curcumin in F508del-CFTR cell lines

Eur J Pharm Biopharm. 2017 Aug:117:168-181. doi: 10.1016/j.ejpb.2017.04.015. Epub 2017 Apr 17.

Abstract

Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2. When used on ΔF508-CFTR cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE fluorescence experiments show that this effect is associated with a correction of a Cl- selective current at the membrane surface of F508del-CFTR cells. The results show the great potential of the neutral amphiphilic triblock copolymer MeOx6-THF19-MeOx6 as carrier for curcumin in a Cystic Fibrosis context. We anticipate that other MeOxn-THFm-MeOxn copolymers could have similar behaviours for other highly insoluble therapeutic drugs or cosmetic active ingredients.

Keywords: Amphiphilic polymer; CFTR; Curcumin; Cystic fibrosis; Triblock copolymer.

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Curcumin / chemistry
  • Curcumin / metabolism*
  • Curcumin / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Compounding
  • Furans / chemistry
  • Furans / metabolism*
  • Furans / pharmacology
  • Humans
  • Mice
  • Oxazoles / chemistry
  • Oxazoles / metabolism*
  • Oxazoles / pharmacology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism*

Substances

  • 2-methyl-2-oxazoline
  • Furans
  • Oxazoles
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • tetrahydrofuran
  • Curcumin