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Novel “plum pudding” gels as potential drug‐eluting stent coatings: Controlled release of fluvastatin
Author(s) -
McGillicuddy F.C.,
Lynch I.,
Rochev Y.A.,
Burke M.,
Dawson K.A.,
Gallagher W.M.,
Keenan A.K.
Publication year - 2006
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.30839
Subject(s) - materials science , copolymer , elution , fluvastatin , diffusion , drug delivery , chemical engineering , drug carrier , chromatography , biomedical engineering , composite material , nanotechnology , chemistry , polymer , pharmacology , medicine , physics , engineering , thermodynamics , simvastatin
Abstract This study evaluated novel structural motifs known as “plum pudding” gels as potential drug‐eluting stent coatings. Controlled delivery of a HMG‐CoA reductase inhibitor (statin) from the intravascular stent surface represents a potential therapeutic modality for prevention of in‐stent restenosis (ISR). In this study, gels were comprised of fluvastatin‐loaded thermoresponsive microgel particles containing the relatively hydrophilic N ‐isopropylacrylamide (NiPAAm), mixed with the more hydrophobic N ‐ tert ‐butylacrylamide (NtBAAm) in different wt/wt ratios: 85/15, 65/35, and 50/50, randomly dispersed in a 65/35 or 85/15 NiPAAm/NtBAAm copolymer matrix. Fluvastatin release from 5 μm copolymer films was greatest from the most hydrophilic systems and least from the more hydrophobic systems. Release from hydrophobic matrices appeared to be via Fickian diffusion, enabling use of the Stokes–Einstein equation to determine diffusion coefficients. Release from hydrophilic matrices was non‐Fickian. Eluted drug retained its bioactivity, assessed as selective inhibition of human coronary artery smooth muscle cell proliferation. When stainless steel stent wires were coated (25 μm thickness) with fluvastatin‐loaded 65/35 microgels in an 85/15 copolymer matrix, drug elution into static and perfused flow environments followed similar elution profiles. In contrast to elution from copolymer films cast on flat surfaces, diffusion from stent wires coated with hydrophilic and hydrophobic systems both followed Fickian patterns, with slightly larger diffusion coefficients for elution from the flow system. We conclude that manipulation of the relative hydrophobicities of both microgel and matrix components of “plum pudding” gels results in tightly regulated release of fluvastatin over an extended time period relevant to initiation and propagation of ISR. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006