An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies

Lihui Weng, Nassir Rostambeigi, Nicole D Zantek, Parinaz Rostamzadeh, Mike Bravo, John Carey, Jafar Golzarian

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17 ± 4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37 C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37 C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.

Original languageEnglish (US)
Pages (from-to)8182-8191
Number of pages10
JournalActa Biomaterialia
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2013

Fingerprint

Hydrogel
Hydrogels
Therapeutics
Tetracycline
Microspheres
oxidized cellulose
Sclerosing Solutions
Carboxymethylcellulose Sodium
Schiff Bases
Catheters
Fluoroscopy
Endothelial cells
Human Umbilical Vein Endothelial Cells
Gelation
Cytotoxicity
Muramidase
Pore structure
Drug delivery
Pharmaceutical Preparations
Doxorubicin

Keywords

  • Carboxymethyl chitosan
  • Drug delivery
  • Embolization
  • Hydrogel
  • In situ forming

Cite this

An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies. / Weng, Lihui; Rostambeigi, Nassir; Zantek, Nicole D; Rostamzadeh, Parinaz; Bravo, Mike; Carey, John; Golzarian, Jafar.

In: Acta Biomaterialia, Vol. 9, No. 9, 01.09.2013, p. 8182-8191.

Research output: Contribution to journalArticle

Weng, Lihui ; Rostambeigi, Nassir ; Zantek, Nicole D ; Rostamzadeh, Parinaz ; Bravo, Mike ; Carey, John ; Golzarian, Jafar. / An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies. In: Acta Biomaterialia. 2013 ; Vol. 9, No. 9. pp. 8182-8191.
@article{47a686cb1e7f4fe1b8a9d5f10bb4be23,
title = "An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies",
abstract = "We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17 ± 4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37 C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30{\%} was observed over 78 h in phosphate-buffered saline at 37 C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8{\%} and 2.1{\%}) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.",
keywords = "Carboxymethyl chitosan, Drug delivery, Embolization, Hydrogel, In situ forming",
author = "Lihui Weng and Nassir Rostambeigi and Zantek, {Nicole D} and Parinaz Rostamzadeh and Mike Bravo and John Carey and Jafar Golzarian",
year = "2013",
month = "9",
day = "1",
doi = "10.1016/j.actbio.2013.06.020",
language = "English (US)",
volume = "9",
pages = "8182--8191",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",
number = "9",

}

TY - JOUR

T1 - An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies

AU - Weng, Lihui

AU - Rostambeigi, Nassir

AU - Zantek, Nicole D

AU - Rostamzadeh, Parinaz

AU - Bravo, Mike

AU - Carey, John

AU - Golzarian, Jafar

PY - 2013/9/1

Y1 - 2013/9/1

N2 - We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17 ± 4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37 C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37 C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.

AB - We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17 ± 4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37 C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37 C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.

KW - Carboxymethyl chitosan

KW - Drug delivery

KW - Embolization

KW - Hydrogel

KW - In situ forming

UR - http://www.scopus.com/inward/record.url?scp=84880922222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880922222&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2013.06.020

DO - 10.1016/j.actbio.2013.06.020

M3 - Article

VL - 9

SP - 8182

EP - 8191

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

IS - 9

ER -