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Poly( N ‐isopropylacrylamide) copolymer films as vehicles for the sustained delivery of proteins to vascular endothelial cells
Author(s) -
Kavanagh C. A.,
Gorelova T. A.,
Selezneva I. I.,
Rochev Y. A.,
Dawson K. A.,
Gallagher W. M.,
Gorelov A. V.,
Keenan A. K.
Publication year - 2004
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.30192
Subject(s) - copolymer , materials science , poly(n isopropylacrylamide) , monomer , nuclear chemistry , vegf receptors , vascular endothelial growth factor , confocal microscopy , polymer , chemistry , biology , composite material , cancer research , microbiology and biotechnology
The aim of this study was to establish the capacity of thermoresponsive poly( N ‐isopropylacrylamide) copolymer films to deliver bioactive concentrations of vascular endothelial growth factor (VEGF 165 ) to human aortic endothelial cells (HAEC) over an extended time period. Films were prepared using a 50:50 (w/w) mixture of non‐crosslinkable and crosslinkable copolymers of the following monomer compositions (w/w): 85:15, N ‐isopropylacrylamide (NiPAAm): N ‐ tert ‐butylacrylamide (NtBAAm); and 85:13:2 NiPAAm:NtBAAm:acrylamidobenzophenone (ABzPh, crosslinking agent), respectively. After crosslinking by UV irradiation, the ability of films to incorporate a fluorescently labeled carrier protein (FITC‐labeled BSA, 1 mg loaded per film), at 4°C, was first established. Incorporation into the matrix was confirmed by the observation that increasing film thickness from 5 to 10 μm increased release from collapsed films at 37°C (1.76 ± 0.15 and 10.98 ± 3.38 μg/mL, respectively, at 24 h postloading) and that this difference was maintained at 5 days postloading (1.81 ± 0.25 and 13.8 ± 2.3 μg/mL, respectively). Incorporation was also confirmed by visualization using confocal microscopy. When 10‐μm films were loaded with a BSA solution (1 mg/mL) containing VEGF 165 (3 μg/mL), sustained release of VEGF 165 was observed (10.75 ± 3.11 ng at 24 h; a total of 31.32 ± 8.50 ng over 7 days). Furthermore, eluted VEGF 165 increased HAEC proliferation by 18.2% over control. The absence of cytotoxic species in medium released from the copolymer films was confirmed by the lack of effect of medium (incubated with copolymer films for 3 days) on HAEC viability. In conclusion this study has shown that NiPAAm:NtBAAm copolymers can be loaded with a therapeutic protein and can deliver bioactive concentrations to human vascular endothelial cells over an extended time period. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 25–35, 2005