title: Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery.
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.
authors.affiliation: Institute For Biomolecules Max Mousseron, Team CRBA, UMR CNRS 5247, University Montpellier 1, Faculty of Pharmacy, 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
authors.forename: Mahfoud
authors.initials: M
authors.lastname: Boustta
authors.affiliation: Department of Surgical Oncology, Montpellier Cancer Institute, ICM Val d'Aurelle, Parc Euromédecine, 34298 Montpellier Cedex 5, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Colombo
authors.affiliation: Institute For Biomolecules Max Mousseron, Team CRBA, UMR CNRS 5247, University Montpellier 1, Faculty of Pharmacy, 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.affiliation: Laboratory of Oncopharmacology, Montpellier Cancer Institute, ICM Val d'Aurelle, Parc Euromédecine, 34298 Montpellier Cedex 5, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Poujol
authors.affiliation: Institute For Biomolecules Max Mousseron, Team CRBA, UMR CNRS 5247, University Montpellier 1, Faculty of Pharmacy, 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France. Electronic address: vertm@univ-montp1.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Vert
mesh_terms: D000085:Acetates / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry*; D000418:Albumins / Q000737:chemistry; D000818:Animals; D003035:Cobalt / Q000737:chemistry; D004396:Coloring Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D020100:Hydrogels; D008751:Methylene Blue / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity; D013645:Tartrazine / Q000737:chemistry; D013696:Temperature
chemical_list: D000085:Acetates; D000180:Acrylic Resins; D000418:Albumins; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; C000591468:poly(N-acryloyl glycinamide); D003035:Cobalt; D013645:Tartrazine; D008751:Methylene Blue
keywords: Gel–sol transition; PNAGA; Poly(N-acryloyl glycinamide); Sustained drug delivery; Thermoresponsive hydrogel; UCST