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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

Millipore
Bifido Selective Supplement B, suitable for microbiology
Supelco
Naproxen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Supelco
5α-Androstan-17β-ol-3-one, VETRANAL®, analytical standard
Sigma-Aldrich
(S)-(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid, 98%
Supelco
Naproxen, VETRANAL®, analytical standard
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, purum, ≥99.0% (TLC)
Sigma-Aldrich
Naproxen, meets USP testing specifications
Diclofenac sodium, European Pharmacopoeia (EP) Reference Standard
USP
Naproxen, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Methanol solution, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Naproxen, European Pharmacopoeia (EP) Reference Standard
USP
Diclofenac sodium, United States Pharmacopeia (USP) Reference Standard
USP
Methyl alcohol, United States Pharmacopeia (USP) Reference Standard
USP
Glacial acetic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Ammonium acetate, BioUltra, ≥99.0%
Supelco
Acetic acid, analytical standard
Supelco
Ammonium acetate, LiChropur, eluent additive for LC-MS
Sigma-Aldrich
Acetic acid, BioUltra, ≥99.5% (GC)
Supelco
Methanol, analytical standard
Sigma-Aldrich
Ammonium acetate solution, BioUltra, ~5 M in H2O
Sigma-Aldrich
Acetic acid, natural, ≥99.5%, FG
Sigma-Aldrich
Acetic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Ammonium acetate, 99.999% trace metals basis
Sigma-Aldrich
Ammonium acetate solution, 7.5 M
Sigma-Aldrich
Ammonium acetate, BioXtra, ≥98%
Sigma-Aldrich
Ammonium acetate, ≥98%
Sigma-Aldrich
Ammonium acetate, reagent grade, ≥98%
Sigma-Aldrich
Diclofenac sodium salt