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  • Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies.

Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies.

Materials science & engineering. C, Materials for biological applications (2015-01-13)
Giuseppe Cirillo, Tania Spataro, Manuela Curcio, U Gianfranco Spizzirri, Fiore Pasquale Nicoletta, Nevio Picci, Francesca Iemma
ABSTRACT

Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are proposed as delivery devices for non-steroidal anti-inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and crosslinker, respectively. Infrared spectroscopy was used to assess the incorporation of monomers into the network, and the network density of hydrogel films was found to strictly depend on both feed composition and film thickness. Calorimetric analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the range 32.8-36.1°C. Equilibrium swelling studies around the LCST allowed the correlation between the structural changes and the temperature variations. The mesh size, indeed, rapidly changed from a collapsed to a swollen state, with beneficial effects in applications such as size-selective permeation or controlled drug delivery, while the crosslinking degree, the film thickness, and the loading method deeply influenced the drug release profiles at 25 and 40°C. The analysis of both 3D-network structure, release kinetics and diffusional constraints at different temperatures was evaluated by mathematical modelling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, suitable for HPLC
Sigma-Aldrich
Acetic acid, ≥99.7%, SAJ super special grade
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Acetic acid, SAJ first grade, ≥99.0%
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Ammonium acetate, JIS special grade, ≥97.0%
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Acetic acid, ≥99.7%
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Ammonium acetate, SAJ first grade, ≥97.0%
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Acetic acid, 99.5-100.0%
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Acetic acid, JIS special grade, ≥99.7%
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Ammonium acetate solution, 50 % (w/v)
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Acetic acid solution, SAJ first grade, 27.0-33.0%
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Acetic acid, ≥99.7%, for titration in non-aqueous medium
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Methanol, SAJ first grade, ≥99.5%
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Ammonium acetate solution, 50 % (w/v), suitable for iron determination
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Methanol, JIS 300, ≥99.8%
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Methanol, JIS special grade, ≥99.8%
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Acetic acid solution, 1 M, 1 N
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Acetic acid-12C2, 99.9 atom % 12C
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Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Supelco
Diclofenac sodium salt, Pharmaceutical Secondary Standard; Certified Reference Material
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N-Isopropylacrylamide, ≥99%
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Ammonium acetate solution, 7.5 M
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Ammonium acetate, ≥98%
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Ammonium acetate, reagent grade, ≥98%
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Ammonium acetate, BioXtra, ≥98%
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Diclofenac sodium salt
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Ammonium acetate, LiChropur, eluent additive for LC-MS
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Acetic acid, BioUltra, ≥99.5% (GC)
Supelco
Methanol, analytical standard
Sigma-Aldrich
Ammonium acetate solution, BioUltra, ~5 M in H2O
Sigma-Aldrich
Ammonium acetate, BioUltra, ≥99.0%