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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

Naproxen, European Pharmacopoeia (EP) Reference Standard
USP
Methyl alcohol, United States Pharmacopeia (USP) Reference Standard
USP
Glacial acetic acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Naproxen, Pharmaceutical Secondary Standard; Certified Reference Material
Millipore
Bifido Selective Supplement B, suitable for microbiology
Supelco
5α-Androstan-17β-ol-3-one, VETRANAL®, analytical standard
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Sigma-Aldrich
(S)-(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid, 98%
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, purum, ≥99.0% (TLC)
Supelco
Naproxen, VETRANAL®, analytical standard
USP
Naproxen, United States Pharmacopeia (USP) Reference Standard
Diclofenac sodium, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, ≥97.5%
Sigma-Aldrich
Naproxen, meets USP testing specifications
USP
Diclofenac sodium, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetic acid-12C2, 99.9 atom % 12C
Sigma-Aldrich
Methanol, NMR reference standard
Sigma-Aldrich
N-Isopropylacrylamide, ≥99%
Supelco
Diclofenac sodium salt, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
N-Isopropylacrylamide, 97%
Sigma-Aldrich
Ammonium acetate solution, BioUltra, for molecular biology, ~5 M in H2O
Supelco
Methanol, analytical standard
Sigma-Aldrich
Acetic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Ammonium acetate solution, for molecular biology, 7.5 M
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, Absolute - Acetone free
Supelco
Diclofenac sodium salt, analytical standard
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%