Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: Effects on restenosis and implications for catheter-based drug delivery

Irmina Gradus-Pizlo, Robert L. Wilensky, Keith L. March, Naomi Fineberg, Marybeth Michaels, George E. Sandusky, David R. Hathaway

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Objectives.: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or a colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. Background.: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. Methods.: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). Results.: Delivery efficiency was 0.01% and intramural retention <24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicines resulted in toxicity to the adjacent musculature. Conclusions.: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

Original languageEnglish (US)
Pages (from-to)1549-1557
Number of pages9
JournalJournal of the American College of Cardiology
Volume26
Issue number6
DOIs
StatePublished - Nov 15 1995

Fingerprint

Colchicine
Catheters
Pharmaceutical Preparations
Angioplasty
Cytotoxins
Femoral Artery
Blood Vessels
Arteries
Cell Proliferation
Rabbits

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue : Effects on restenosis and implications for catheter-based drug delivery. / Gradus-Pizlo, Irmina; Wilensky, Robert L.; March, Keith L.; Fineberg, Naomi; Michaels, Marybeth; Sandusky, George E.; Hathaway, David R.

In: Journal of the American College of Cardiology, Vol. 26, No. 6, 15.11.1995, p. 1549-1557.

Research output: Contribution to journalArticle

Gradus-Pizlo, Irmina ; Wilensky, Robert L. ; March, Keith L. ; Fineberg, Naomi ; Michaels, Marybeth ; Sandusky, George E. ; Hathaway, David R. / Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue : Effects on restenosis and implications for catheter-based drug delivery. In: Journal of the American College of Cardiology. 1995 ; Vol. 26, No. 6. pp. 1549-1557.
@article{16a269b9619f4bac8b862ebc28aa75b1,
title = "Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: Effects on restenosis and implications for catheter-based drug delivery",
abstract = "Objectives.: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or a colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. Background.: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. Methods.: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). Results.: Delivery efficiency was 0.01{\%} and intramural retention <24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicines resulted in toxicity to the adjacent musculature. Conclusions.: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.",
author = "Irmina Gradus-Pizlo and Wilensky, {Robert L.} and March, {Keith L.} and Naomi Fineberg and Marybeth Michaels and Sandusky, {George E.} and Hathaway, {David R.}",
year = "1995",
month = "11",
day = "15",
doi = "10.1016/0735-1097(95)00345-2",
language = "English (US)",
volume = "26",
pages = "1549--1557",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "6",

}

TY - JOUR

T1 - Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue

T2 - Effects on restenosis and implications for catheter-based drug delivery

AU - Gradus-Pizlo, Irmina

AU - Wilensky, Robert L.

AU - March, Keith L.

AU - Fineberg, Naomi

AU - Michaels, Marybeth

AU - Sandusky, George E.

AU - Hathaway, David R.

PY - 1995/11/15

Y1 - 1995/11/15

N2 - Objectives.: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or a colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. Background.: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. Methods.: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). Results.: Delivery efficiency was 0.01% and intramural retention <24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicines resulted in toxicity to the adjacent musculature. Conclusions.: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

AB - Objectives.: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or a colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. Background.: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. Methods.: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). Results.: Delivery efficiency was 0.01% and intramural retention <24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicines resulted in toxicity to the adjacent musculature. Conclusions.: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

UR - http://www.scopus.com/inward/record.url?scp=0028818348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028818348&partnerID=8YFLogxK

U2 - 10.1016/0735-1097(95)00345-2

DO - 10.1016/0735-1097(95)00345-2

M3 - Article

C2 - 7594084

AN - SCOPUS:0028818348

VL - 26

SP - 1549

EP - 1557

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 6

ER -