NaCl-triggered self-assembly of hydrophilic poloxamine block copolymers

Int J Pharm. 2015 Oct 15;494(1):453-62. doi: 10.1016/j.ijpharm.2015.08.058. Epub 2015 Aug 24.

Abstract

Tetronic 1307 (T1307) is a hydrophilic poloxamine (HLB>24) with a high molecular mass owing to its long PEO and PPO blocks. In spite of good biocompatibility, its use as a component of drug delivery systems is limited by its high critical micelle concentration (CMC) and temperature (CMT). The aim of this work was to elucidate whether the addition of NaCl or the combination of salts and temperature may bring T1307 micellization and gelling features into more practically useful values. Increasing NaCl concentration in the 0.154 M (isotonic) to 2M (hypertonic) range made the copolymer more hydrophobic and more prone to self-assemble into unimodal micelles, as observed by means of π-A isotherms, (1)H NMR, dynamic light scattering (DLS), small-angle neutron scattering (SANS), and pyrene fluorescence. The decrease in CMC and CMT observed for T1307 in 0.5 M NaCl medium (tolerable hypertonic solution), compared to water, notably favored the solubility of hydrophobic drugs such as curcumin and quercetin. Moreover, phase diagram, intrinsic viscosity and sol-to-gel transition were markedly affected by NaCl concentration. Overall, the strong dependence of T1307 self-assembly features on NaCl opens interesting possibilities for tuning the performance of T1307 as a component of nanocarriers and in situ gelling systems.

Keywords: Block copolymers; Drug solubility; In situ gelling; Micelles; Osmolarity; Salt concentration; Self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Curcumin / chemistry
  • Drug Delivery Systems*
  • Drug Stability
  • Ethylenediamines / chemistry*
  • Hydrophobic and Hydrophilic Interactions*
  • Light
  • Micelles*
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Neutron Diffraction
  • Polyamines / chemistry*
  • Polymers / chemistry*
  • Quercetin / chemistry
  • Scattering, Small Angle
  • Sodium Chloride / chemistry*
  • Solubility
  • Temperature
  • Viscosity

Substances

  • Ethylenediamines
  • Micelles
  • Polyamines
  • Polymers
  • Tetronic 1307
  • Sodium Chloride
  • Quercetin
  • Curcumin