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Novel "plum pudding" as potential drug-eluting stent coatings : Controlled release of fluvastatin

McGillicuddy, F. C. ; Lynch, Iseult LU ; Rochev, Y. A. ; Burke, M. ; Dawson, K. A. ; Gallagher, W. M. and Keenan, A. K. (2006) In Journal of Biomedical Materials Research. Part A 79A(4). p.923-933
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-isopropyl-acrylamide (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 mu m copolymer films was greatest from the most hydrophilic systems... (More)
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-isopropyl-acrylamide (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 mu m 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 nonFickian. Fluted drug retained its bioactivity, assessed as selective inhibition of human coronary artery smooth muscle cell proliferation. When stainless steel stent wires were coated (25 mu m 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. (c) 2006 Wiley Periodicals, Inc. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fluvastatin, local drug delivery, stent wires, NiPAAm/NtBAAm, microgels
in
Journal of Biomedical Materials Research. Part A
volume
79A
issue
4
pages
923 - 933
publisher
John Wiley and Sons
external identifiers
  • wos:000242360400017
  • scopus:33845494732
ISSN
1552-4965
DOI
10.1002/jbm.a.30839
language
English
LU publication?
yes
id
b31746cc-9730-4dc9-a516-5bc8ea3c11be (old id 685477)
date added to LUP
2016-04-01 12:15:58
date last changed
2021-04-13 02:00:37
@article{b31746cc-9730-4dc9-a516-5bc8ea3c11be,
  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-isopropyl-acrylamide (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 mu m 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 nonFickian. Fluted drug retained its bioactivity, assessed as selective inhibition of human coronary artery smooth muscle cell proliferation. When stainless steel stent wires were coated (25 mu m 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. (c) 2006 Wiley Periodicals, Inc.},
  author       = {McGillicuddy, F. C. and Lynch, Iseult and Rochev, Y. A. and Burke, M. and Dawson, K. A. and Gallagher, W. M. and Keenan, A. K.},
  issn         = {1552-4965},
  language     = {eng},
  number       = {4},
  pages        = {923--933},
  publisher    = {John Wiley and Sons},
  series       = {Journal of Biomedical Materials Research. Part A},
  title        = {Novel "plum pudding" as potential drug-eluting stent coatings : Controlled release of fluvastatin},
  url          = {http://dx.doi.org/10.1002/jbm.a.30839},
  doi          = {10.1002/jbm.a.30839},
  volume       = {79A},
  year         = {2006},
}