The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor

J Control Release. 2015 Aug 28:212:41-9. doi: 10.1016/j.jconrel.2015.06.013. Epub 2015 Jun 14.

Abstract

Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions.

Keywords: Blood-vessel-embolic materials; Controlled release; Doxorubicin; TACE; Temperature sensitive nanogels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Cell Survival / drug effects
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Delivery Systems*
  • Embolization, Therapeutic
  • Female
  • Gels
  • Hep G2 Cells
  • Humans
  • Iohexol / administration & dosage
  • Iohexol / chemistry
  • Liver Neoplasms / therapy*
  • Male
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Polymethacrylic Acids / chemistry
  • Rabbits
  • Renal Artery
  • Temperature

Substances

  • Acrylic Resins
  • Antibiotics, Antineoplastic
  • Contrast Media
  • Gels
  • Polymethacrylic Acids
  • poly-N-isopropylacrylamide
  • Iohexol
  • Doxorubicin
  • polybutyl methacrylate