Controlled release of paclitaxel from heparinized metal stent fabricated by layer-by-layer assembly of polylysine and hyaluronic acid-g-poly(lactic-co- glycolic acid) micelles encapsulating paclitaxel

Gyoung Kim Taek, Hyukjin Lee, Yangsoo Jang, Gwan Park Tae

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Drug-eluting stent (DES) has been widely used for effective treatment of obstructive coronary artery disease, preventing the occurrence of restenosis that is mainly caused by hyper-proliferation of smooth muscle cells. Here, we demonstrate the immobilization of heparin on the metal surface via a bioinspired manner and subsequent build-up of a therapeutic layer-by-layer multilayer composed of paclitaxel (PTX) encapsulated poly(lactic-coglycolic acid) grafted hyaluronic acid (HA-g-PLGA) micelles, heparin, and poly-L-lysine (PLL). It was hypothesized that the heparinized metallic surface would create a nonthrombogenic environment, while controlled release of PTX from the surface could induce antiproliferation of smooth muscle cells. For the surface immobilization of heparin on the surface of cobalt-chromium alloy (L605), dopamine-derivatized heparin was synthesized and anchored on the surface by a mussel-inspired adhesion mechanism. An amphiphilic graft copolymer of HA-g-PLGA was synthesized and utilized for the formation of anionic PTX loaded micelles. A PTX eluting multilayer composed of anionic HA-g-PLGA micelles, heparin, and PLL was self-assembled on the metal surface by a layer-by-layer fashion. The loading amount of PTX on the metal surface could be readily controlled with concomitantly achieving sustained release profiles of PTX over an extended period. The proliferation of human coronary artery smooth muscle cells was successfully arrested by controlled released PTX from the therapeutic multilayer coated on the metallic substrate.

Original languageEnglish
Pages (from-to)1532-1539
Number of pages8
JournalBiomacromolecules
Volume10
Issue number6
DOIs
Publication statusPublished - 2009 Jun 8

Fingerprint

Hyaluronic acid
Polylysine
Stents
Micelles
Hyaluronic Acid
Paclitaxel
Metals
Acids
Heparin
Muscle
Multilayers
Cells
Lysine
Chromium Alloys
Cobalt alloys
Chromium alloys
polylactic acid-polyglycolic acid copolymer
Milk
Graft copolymers
Lactic acid

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

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abstract = "Drug-eluting stent (DES) has been widely used for effective treatment of obstructive coronary artery disease, preventing the occurrence of restenosis that is mainly caused by hyper-proliferation of smooth muscle cells. Here, we demonstrate the immobilization of heparin on the metal surface via a bioinspired manner and subsequent build-up of a therapeutic layer-by-layer multilayer composed of paclitaxel (PTX) encapsulated poly(lactic-coglycolic acid) grafted hyaluronic acid (HA-g-PLGA) micelles, heparin, and poly-L-lysine (PLL). It was hypothesized that the heparinized metallic surface would create a nonthrombogenic environment, while controlled release of PTX from the surface could induce antiproliferation of smooth muscle cells. For the surface immobilization of heparin on the surface of cobalt-chromium alloy (L605), dopamine-derivatized heparin was synthesized and anchored on the surface by a mussel-inspired adhesion mechanism. An amphiphilic graft copolymer of HA-g-PLGA was synthesized and utilized for the formation of anionic PTX loaded micelles. A PTX eluting multilayer composed of anionic HA-g-PLGA micelles, heparin, and PLL was self-assembled on the metal surface by a layer-by-layer fashion. The loading amount of PTX on the metal surface could be readily controlled with concomitantly achieving sustained release profiles of PTX over an extended period. The proliferation of human coronary artery smooth muscle cells was successfully arrested by controlled released PTX from the therapeutic multilayer coated on the metallic substrate.",
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