Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery

J Control Release. 2014 Jan 28:174:1-6. doi: 10.1016/j.jconrel.2013.10.040. Epub 2013 Nov 8.

Abstract

Poly(N-acryloyl glycinamide) is a neutral polymer that can form gel-sol thermoresponsive systems with upper critical solution temperature in aqueous media. The temperature of the reversible gel-sol transition depends on the molar mass and the concentration of macromolecules. These parameters were combined to adjust the transition temperature slightly above body temperature for the sake of respecting living tissues during the sol form injection using a classical syringe. On contact with local tissues, the injected sol turned rapidly to a gel. The simplicity of the process makes it exploitable to administrate and deliver neutral or ionic drug and especially those that are soluble in aqueous media. The versatility was exemplified from formulations with cobalt acetate, small polymers (MW~2000g/mol), tartrazine and methylene blue dyes and albumin. The model compounds were allowed to diffuse in an isotonic pH=7.4 buffered medium at 37°C. All the release profiles were typical of diffusion control with 100% release within 2 to 3weeks and no obvious burst. The in vitro release of methylene blue from a gel formulation was checked prior to injection in the peritoneal cavity of mice where the release of the dye was monitored visually through tissue and organ colorations. A comparable polymer-free dye solution was used as control. Coloration appeared rapidly in tissues and organs and it was still detectable 52h post injection of the gel whereas it was no longer present at 24h in control mice.

Keywords: Gel–sol transition; PNAGA; Poly(N-acryloyl glycinamide); Sustained drug delivery; Thermoresponsive hydrogel; UCST.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acrylic Resins / chemistry*
  • Albumins / chemistry
  • Animals
  • Cobalt / chemistry
  • Coloring Agents / administration & dosage
  • Coloring Agents / chemistry
  • Coloring Agents / pharmacokinetics
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Delivery Systems*
  • Female
  • Hydrogels
  • Methylene Blue / administration & dosage
  • Methylene Blue / chemistry
  • Methylene Blue / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Cavity
  • Tartrazine / chemistry
  • Temperature

Substances

  • Acetates
  • Acrylic Resins
  • Albumins
  • Coloring Agents
  • Delayed-Action Preparations
  • Hydrogels
  • poly(N-acryloyl glycinamide)
  • Cobalt
  • Tartrazine
  • Methylene Blue