Abstract
The aim of this study was to establish the capacity of thermoresponsive poly(N‐isopropylacrylamide) copolymer films to deliver bioactive concentrations of an antimitotic agent to human vascular smooth muscle cells (HASMC) over an extended period of time. Copolymer films were prepared using a 50:50 (w/w) ratio of N‐isopropylacrylamide (NiPAAm) monomer to the more hydrophobic N‐tert‐butylacrylamide (NtBAAm) and loaded with the antimitotic agent colchicine (0.1 μmol per film) at room temperature. Colchicine release from films was sustained over a 14‐day period. At 24 h postloading, the concentration of colchicine in the medium overlying films was 2.12 ± 0.16 μ__M__; this fell to 0.20 ± 0.01 μ__M__ at 7 days and decreased further to 0.12 ± 0.01 μ__M__ after 14 days. Colchicine released from copolymer films inhibited proliferation when subsequently placed on HASMC: at 0.1 μ__M__, released colchicine reduced proliferation to 18.5 ± 0.8% of control cells (p < 0.001, n = 9). The antiproliferative effect of released colchicine was comparable to that of native colchicine, as observed in separate experiments. Furthermore, colchicine released from 50:50 polymer films inhibited the proliferation of cells grown in the same environment as the copolymer. Inhibition of cell proliferation was not due to the release of cytotoxic particles from the copolymer because medium incubated with copolymer for 5 days and then applied to HASMC did not alter cell viability. In conclusion, this study demonstrates that 50:50 NiPAAm:NtBAAm copolymers can deliver bioactive concentrations of the antimitotic agent colchicine to human vascular cells over an extended period of time. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 667–673, 2003